COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants.

BACKGROUND: During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11-28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. METHODS: This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. RESULTS: 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4-7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. CONCLUSION: This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.

Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variants BA.2, BA.5 and BQ.1.1 in critically ill patients with COVID-19: a prospective, multicenter cohort study.

BACKGROUND: Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality. RESULTS: The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as "BA.2" (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as "BA.4/BA.5", and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as "BQ.1.1". The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up. CONCLUSIONS: Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference.

Fatal neonatal listeriosis following L. monocytogenes horizontal transmission highlights neonatal susceptibility to orally acquired listeriosis.

We report a case of fulminant fatal neonatal listeriosis due to horizontal transmission of Listeria monocytogenes (Lm) in a neonatal double room. Genomic analyses reveal a close genetic relationship between clinical isolates, supporting cross-contamination. Oral inoculation experiments in adult and neonatal mice show that neonates are susceptible to a low Lm inoculum and that this susceptibility results from the immaturity of the neonatal gut microbiota. Infected neonates should therefore be isolated for as long as they shed Lm in their feces to avoid horizontal transmission and its dire consequences.

Factors associated with delay in seeking healthcare for imported malaria: a retrospective study in a French hospital.

BACKGROUND: Delayed treatment is associated with a higher risk of severe malaria. In malaria-endemic areas, the main factors associated with delay in seeking healthcare are low educational level and traditional beliefs. In imported malaria, determinants of delay in seeking healthcare are currently unknown. METHODS: We studied all patients presenting with malaria, from 1 January 2017 to 14 February 2022, in the hospital of Melun, France. Demographic and medical data were recorded for all patients, and socio-professional data were recorded for a subgroup of hospitalized adults. Relative-risks and 95% confidence intervals were determined using univariate analysis by cross-tabulation. RESULTS: There were 234 patients included, all travelling from Africa. Among them, 218 (93%) were infected with P. falciparum, 77 (33%) had severe malaria, 26 (11%) were <18 years old and 81 were included during the SARS-CoV-2 pandemic. There were 135 hospitalized adults (58% of all patients). The median time to hospital admission (THA) , defined by the period from onset of symptoms to arrival at hospital, was 3 days (IQR = 2-5). A THA ≥3 days tended to be more frequent in travellers visiting friends and relatives (VFR; RR = 1.44, 95% CI = [1.0-2.05], P = 0.06), while it was less frequent in children and teenagers (RR = 0.58, 95% CI = [0.39-0.84], P = 0.01). Gender, African background, unemployment, living alone and absence of referring physician were not associated with delay in seeking healthcare. Consulting during the SARS-CoV-2 pandemic was neither associated with a longer THA nor with a higher rate of severe malaria. CONCLUSION: In contrast to an endemic area, socio-economic factors did not impact on delay in seeking healthcare in imported malaria. Prevention should focus on VFR subjects, who tend to consult later than other travellers.

Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19.

Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) is different from that in those infected with variant Delta (n = 111). We observe no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35-1.32]; p = 0.253). Among Omicron-infected patients, 43.2% are immunocompromised, most of whom have received two doses of vaccine or more (85.9%) but display a poor humoral response to vaccination. The mortality rate of immunocompromised patients infected with variant Omicron is significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there is no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms/mutational profile and 28-day mortality.

Association of high SARS-CoV-2 RNAemia with diabetes and mortality in critically ill COVID-19 patients.

It has been suggested that during the period of respiratory worsening of severe COVID-19 patients, viral replication plays a less important role than inflammation. Using the droplet-based digital PCR (ddPCR) for precise quantification of plasma SARS-CoV-2 viral load (SARS-CoV-2 RNAemia), we investigated the relationship between plasma viral load, comorbidities, and mortality of 122 critically ill COVID-19 patients. SARS-CoV-2 RNAemia was detected by ddPCR in 90 (74%) patients, ranging from 70 to 213,152 copies per mL. A high (>1 000 copies/ml) or very high (>10,000 copies/ml) SARS-Cov-2 RNAemia was observed in 46 patients (38%), of which 26 were diabetic. Diabetes was independently associated with a higher SARS-CoV-2 RNAemia. In multivariable logistic regression models, SARS-CoV-2 RNAemia was strongly and independently associated with day-60 mortality. Early initiation of antiviral therapies might be considered in COVID-19 critically ill patients with high RNAemia.

Risk of Multidrug Resistant Bacteria Acquisition in Patients with Declared ß-Lactam Allergy during Hospitalization in Intensive Care Unit: A Retrospective Cohort Study (2007-2018).

INTRODUCTION: The risk of extended spectrum ß-lactamase (ESBL) bacterial acquisition in patients with ß-lactam allergy has been poorly investigated. In a previous study conducted over a 6-year long period (2007-2012), we found that patients with declared ß-lactam allergy had a higher risk of ESBL bacterial carriage at admission in intensive care unit (ICU), but they had not a higher risk of ESBL bacterial acquisition. We present the final results of the study which was eventually conducted over a 12-year long period (2007-2018). MATERIALS AND METHODS: The study included all patients admitted in ICU and receiving antibiotic treatment from January 2007 to December 2018. ESBL bacterial acquisition was the main clinical outcome. Mortality in ICU, multidrug resistant bacterial carriage at admission and discharge were the secondary outcomes. RESULTS: Overall, 3332 patients were included, 132/3332 (3.9%) were labelled ß-lactam allergic, while 3200/3332 (96.1%) did not presented ß-lactam allergy. No significant difference in rates of ESBL acquisition was detected (4/132, 3% vs. 78/3200, 2.4%; p = 0.17). Patients with ß-lactam allergy had higher rates of ESBL bacterial carriage at admission (19/132, 14.4% vs. 248/3200, 7.8%, p = 0.01) and at discharge (22/132, 16.7% vs. 351/3200, 11%, p = 0.04) than nonallergic patients. No differences in mortality, duration of hospitalization, and carriage of methicillin resistant Staphylococcus aureus were reported. Female gender was the only factor associated with ß-lactam allergy at the multivariate analysis. CONCLUSIONS: This study confirms that patients with declared ß-lactam allergy had not a higher risk of ESBL bacterial acquisition during hospitalization in ICU. However, they had a higher ESBL bacterial carriage at admission.

Bacterial Epidemiology of Surgical Site Infections after Open Fractures of the Lower Limb: A Retrospective Cohort Study.

Open lower limb fractures are common injuries, and the occurrence of infectious complications after open fractures is a usual problem. The rate of surgical site infections (SSIs) and the nature and resistance of the germs responsible for SSIs remain poorly described. Our aim was to describe the bacterial epidemiology of SSIs after surgical management of an open lower limb fracture. We conducted a retrospective monocentric cohort study from 1 January 2012 to 31 December 2020 based on the analysis of inpatient records in a non-university hospital of Ile de France region. All patients who underwent surgery for an open lower limb fracture were included. A total of 149 patients were included. In our population, 19 (12.7%) patients developed an SSI. Of these 19 patients, the sample was polymicrobial in 9 (47.4%) patients. In 9 (45%) cases, the samples identified a group 3 enterobacteria, Enterobacter cloacae being the main one in 7 (36.9%) cases. Staphylococci were identified in 11 patients, with Staphylococcus aureus in 9 (47.4%). All Staphylococcus aureus were susceptible to methicillin, and all enterobacteria were susceptible to C3G. Among all SSI, 10 (58.8%) contained at least one germ resistant to amoxicillin/clavulanic acid (AMC). The SSIs rate was 12.7%. The main pathogens identified were Enterobacter cloacae and Staphylococcus aureus. The presence of early SSI caused by group 3 Enterobacteriaceae renders current antibiotic prophylaxis protocols inadequate with AMC in half the cases.

Ventilator-Associated Pneumonia in COVID-19 Patients: A Retrospective Cohort Study.

INTRODUCTION: Aim of this study is to analyse the characteristics of ventilator-associated pneumonia (VAP) inpatients infected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). MATERIALS AND METHODS: A retrospective study was conducted, including coronavirus infectious disease 2019 (COVID-19) patients who developed VAP from March to May 2020 (VAP COVID-19). They were compared to non-COVID-19 patients who developed VAP from January 2011 to December 2019 (VAP NO COVID-19) and COVID-19 patients who did not develop VAP (NO VAP COVID-19). RESULTS: Overall, 42 patients were included in the VAP COVID-19group, 37 in the NO VAP COVID-19 group, and 188 in the VAP NO COVID-19 group. VAP COVID-19 had significantly higher rates of shock (71% vs. 48%, p = 0.009), death in ICU (52% vs. 30%, p = 0.011), VAP recurrence (28% vs. 4%, p < 0.0001), positive blood culture (26% vs. 13%, p = 0.038), and polymicrobial culture (28% vs. 13%, p = 0.011) than VAP NO COVID-19. At the multivariate analysis, death in patients with VAP was associated with shock (p = 0.032) and SARS-CoV-2 (p = 0.008) infection. CONCLUSIONS: VAP in COVID-19 patients is associated with shock, bloodstream, and polymicrobial infections.

Trimethoprim-sulfamethoxazole as de-escalation in ventilator-associated pneumonia: a cohort study subanalysis.

PURPOSE: This is a subanalysis of a previous study which compared the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) with all other regimens for treatment of ventilator-associated pneumonia (VAP). Aim of the current study was to focus on the effectiveness of a strategy based on TMP-SMX as de-escalation from ß-lactam including regimens. METHODS: Retrospective cohort study including patients who were hospitalized for VAP from 2011 to 2019. Patients were distributed in two groups: NO SWITCH TO TMP-SMX group, including patients who received ß-lactams for all treatment duration, and SWITCH TO TMP-SMX group, which included patients who switched to TMP-SMX from a ß-lactam including regimen after microbiology diagnosis. Three clinical outcomes were analyzed: mortality at 30 days from the start of the antibiotic treatment (T30), mortality at the end of treatment (EoT), and acquisition of multidrug-resistant bacteria during hospitalization in intensive care unit. RESULTS: Overall, 70 patients were included in the current study, 32/70 (45.7%) in NO SWITCH TO TMP-SMX group and 38/70 (54.3%) in SWITCH TO TMP-SMX group, 37/70 (52.8%) had been already included in the previous study. No significant differences in clinical outcomes and patient's characteristics were found when the two groups were compared. CONCLUSIONS: De-escalation to TMP-SMX for VAP treatment was not associated with higher mortality at EoT and T30 than standard treatment with ß-lactam. Monotherapy with TMP-SMX as de-escalation from broad-spectrum empirical regimens is a ß-lactam sparing strategy worthy to be further investigated in either multicenter cohort studies or randomized clinical trials.

ß-Lactam allergy and risk of multidrug-resistant bacteria in the intensive care unit: A cohort study.

Patients identified as allergic to ß-lactams are frequently exposed to treatment with broad-spectrum antibiotics. However, the risk of carriage of extended-spectrum ß-lactamase (ESBL)-producing isolates in this population has been poorly investigated. The aim of this study was to evaluate the characteristics and clinical outcomes of patients admitted to the intensive care unit (ICU) with and without declared ß-lactam allergy at admission. A retrospective monocentric study was performed including adult patients admitted to the ICU between 2007 and 2012. The presence of multidrug-resistant bacteria was documented in rectal and nasal swabs at admission and discharge. Patients labelled allergic to ß-lactams and unlabelled patients were compared. Patients labelled allergic had significantly higher rates of ESBL at admission (13.3% vs. 4.3%; P = 0.0220) and discharge (20.0% vs. 9.0%; P = 0.0460) compared with unlabelled patients, but no significant difference in rates of ESBL acquisition in the ICU was detected. No differences in mortality, duration of hospitalisation or typical risk factors for ESBL acquisition (intubation, central venous catheter and duration of hospitalisation) were reported. No differences in carriage of methicillin-resistant Staphylococcus aureus were detected. This study showed that patients with declared ß-lactam allergy had a higher risk of ESBL carriage at ICU admission and discharge.

False-positive of blood culture instrument: leukocytosis, overfilled vials or defective position?

Continuous monitoring of the performances of blood culture instrument can be based on the indicators proposed by the QUAMIC. Of these, the analytic performance indicator evaluates the rate of false-positive vials. False-positives vials can be reported by the device in case of leukocytosis or when vials are overfilled. In our laboratory, we record prospectively in our software all false positive vials as well as the position used for their incubation. These data are analyzed at least twice a year. For the first half of 2016, this strategy allowed us to identify a defective position. We then evaluated the impact of this anomaly as very weak. The one-year follow-up after the position repair confirmed a correction of the problem. Thus, traceability of positions reporting unexplained false-positive vials (i.e. neither due to leukocytosis nor overfilled vials) can allow laboratories to identify a defective position. This survey, if done prospectively, is simple to perform and not time-consuming. It could usefully complement the analytical performance indicator based on the false-positive rate.

Trimetoprim-sulfametoxazole in ventilator-associated pneumonia: a cohort study.

To evaluate the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) for treatment of ventilator-associated pneumonia (VAP). A retrospective cohort study including patients with VAP from 2011 to 2017. Two groups were analysed: TMP-SMX group, including patients who had received TMP-SMX (as first-line and as de-escalation), and No-TMP-SMX group, including patients who had not received TMP-SMX treatment. Primary clinical outcome was mortality at 30 days from starting the antibiotic treatment (T30). Secondary outcomes were mortality at end of treatment (EoT), day survival at T30, and acquisition of multidrug-resistant bacteria during hospitalization in intensive care unit. Eighty cases of VAP were included and devised into two groups: No-TMP-SMX (31/80; 39%) and TMP-SMX (49/80; 61%). Univariate analysis showed no significant differences were found when the TMP-SMX group was compared with the No-TMP-SMX group, except for frequency of male gender (p = 0.025). No significant statistical correlations between mortality at T30 and individual factors were detected by the multivariate model. No cases of either severe allergy or Clostridium difficile disease were reported in the TMP-SMX and No-TMP-SMX groups. TMP-SMX treatment was not associated with higher mortality at EoT and T30 in comparison with the No-TMP-SMX group. TMP-SMX had a good safety profile, in terms of ecology (acquisition of MDR bacteria and Clostridium difficile disease) and clinical management (no allergy events).

Impact of a multimodal strategy combining a new standard of care and restriction of carbapenems, fluoroquinolones and cephalosporins on antibiotic consumption and resistance of Pseudomonas aeruginosa in a French intensive care unit.

This study aimed to assess whether post-prescription review and feedback (PPRF) of all antibiotics, with restriction of carbapenems, fluoroquinolones and third-generation cephalosporins (3GCs), along with a change in medical standard of care impacted antibiotic consumption and bacterial antimicrobial resistance in a French medical/surgical intensive care unit (ICU). A 4-year before (2007-2010) and after (2011-2014) retrospective comparative study was performed. Antibiotic consumption was evaluated in defined daily doses per 1000 patient-days. The rates of Pseudomonas aeruginosa resistance to piperacillin, ceftazidime, ciprofloxacin, imipenem and amikacin and of AmpC-hyperproducing group 3 Enterobacteriaceae were assessed. Consumption of fluoroquinolones decreased by -85%, carbapenems by -58%, 3GCs by -50% and glycopeptides by -66% (P ≤ 0.0001). Consumption of penicillins with and without ß-lactamase inhibitors increased by +72% and +78%, sulfonamides by +172% and macrolides by +267% (P < 0.0001). Pseudomonas aeruginosa resistance rates for all antibiotics tested and the proportion of AmpC-hyperproducing group 3 Enterobacteriaceae decreased (P ≤ 0.01). The median length of stay, use of vasopressors and invasive mechanical ventilation decreased, and the use of renal replacement therapy increased (P < 0.05). The initial severity score (SAPS II) increased (P < 0.01) due to changes in practice, with no impact on in-hospital mortality (P = 0.07). In conclusion, changes in medical care along with PPRF and a restriction of high ecological impact antibiotics were associated with a shift towards the consumption of low ecological impact antibiotics in an ICU. Rates of resistant P. aeruginosa and of AmpC-hyperproducing group 3 Enterobacteriaceae decreased simultaneously.

Detection of Fusobacterium nucleatum in culture-negative brain abscess by broad-spectrum bacterial 16S rRNA Gene PCR.

BACKGROUND: Fusobacterium nucleatum is a strict anaerobic microorganism commensal to the human oropharynx and gastrointestinal tract, which causes a wide spectrum of human diseases and it is an important pathogen in abscesses. CASE PRESENTATION: We report the case of a previously healthy 64-year-old woman with multiple abscesses due to Fusobacterium nucleatum, involving liver, pleura and brain. Fusobacterium was not recovered from blood cultures nor from culture of hepatic, pleural and brain drain fluid. The diagnosis was obtained by polymerase chain reaction amplification of bacterial deoxyribonucleic acid in brain abscess drain. CONCLUSIONS: Fusobacterium spp., should be considered in patients with any organ abscess, especially in case of invasive disease with multiple secondary site involving brain. MOLECULAR: techniques might be of special usefulness in cases that remain negative in culture to obtain the diagnosis and perform adequate treatment.