MPox virus: an unusual aetiology of peritonitis.

We describe a rare case of severe disseminated monkeypox (MPox) virus infection complicated by peritonitis in a 44-year-old man living with well-controlled HIV. The patient was successfully treated with tecovirimat without requiring surgery. MPox should be considered in the differential diagnosis of non-bacterial peritonitis in patients at risk of infection.

24/7 workflow for bloodstream infection diagnostics in microbiology laboratories: the first step to improve clinical management.

OBJECTIVES: We aimed to evaluate the impact of an uninterrupted workflow regarding blood cultures on turnaround time and antibiotic prescription. METHODS: Monomicrobial episodes of bacteremia were retrospectively evaluated before and after a continuous 24/7 workflow was implemented in our clinical microbiology laboratory (pre- and post-intervention periods; PREIP and POSTIP). Primary outcome was the time from specimen collection to the first change in antibiotic therapy. Secondary outcomes included the time from specimen collection to effective antibiotic therapy and to antibiotic susceptibility testing results (or turnaround time), as well as hospital length of stay and all-cause mortality at 30 days. RESULTS: A total of 548 episodes of bacteremia were included in the final analysis. There was no difference in PREIP and POSTIP regarding patient characteristics and causative bacteria. In POSTIP, the mean time to the first change in antibiotic therapy was reduced by 10.4 h (p<0.001). The time to effective antibiotic therapy and the turnaround time were respectively reduced by 4.8 h (p<0.001) and 5.1 h (p=0.006) in POSTIP. There was no difference in mean hospital length of stay or mortality between the two groups. CONCLUSIONS: Around the clock processing of blood cultures allows for a reduction in turnaround time, which in turn reduces the delay until effective antibiotic therapy prescription.

Correlations between Persistent Olfactory and Semantic Memory Disorders after SARS-CoV-2 Infection.

Background: One of the main symptoms of COVID-19 is hyposmia or even anosmia. Olfactory identification is most often affected. In addition, some cognitive disorders tend to appear following the infection, particularly regarding executive functions, attention, and memory. Olfaction, and especially olfactory identification, is related to semantic memory which manages general knowledge about the world. The main objective of this study was to determine whether semantic memory is impaired in case of persistent post COVID-19 olfactory disorders. Methods: 84 patients (average age of 42.8 ± 13.6 years) with post COVID-19 olfactory loss were included after consulting to the ENT department. The clinical evaluation was carried out with the Pyramid and Palm Tree Test, the word-retrieval task from the Grémots, the Sniffin' Sticks Test and the Computerised Olfactory Test for the Diagnosis of Alzheimer's Disease. Results: Semantic memory was impaired in 20% (n = 17) of patients, especially in the 19-39 age-group. The olfactory threshold was only significantly correlated with the semantic memory scores. Conclusions: Similar to all cognitive disorders, semantic disorders can have a negative impact on quality of life if left untreated. It is essential to carry out specific assessments of post COVID-19 patients to accurately determine their disorders and to put in place the best possible rehabilitation, such as speech and language therapy, to avoid quality-of-life impairment.

Olfactory Training in Post-COVID-19 Persistent Olfactory Disorders: Value Normalization for Threshold but Not Identification.

(1) Background: Persistent post-viral olfactory disorders (PPVOD) are estimated at 30% of patients one year after COVID-19 infection. No treatment is, to date, significantly effective on PPVOD with the exception of olfactory training (OT). The main objective of this work was to evaluate OT efficiency on post-COVID-19 PPVOD. (2) Methods: Consecutive patients consulting to the ENT department with post-COVID-19 PPVOD were included after completing clinical examination, the complete Sniffin' Stick Test (TDI), the short version of the Questionnaire of olfactory disorders and the SF-36. Patients were trained to practice a self-olfactory training with a dedicated olfactory training kit twice a day for 6 months before returning to undergo the same assessments. (3) Results: Forty-three patients were included and performed 3.5 months of OT in average. We observed a significant TDI score improvement, increasing from 24.7 (±8.9) before the OT to 30.9 (±9.8) (p < 0.001). Based on normative data, a significant increase in the number of normosmic participants was observed only for the threshold values (p < 0.001). Specific and general olfaction-related quality of life improved after the OT. (4) Conclusions: Olfactory function appeared to improve only in peripheral aspects of post-COVID-19 PPVOD after OT. Future controlled studies must be performed to confirm the OT role and justify new therapeutic strategies that may focus on the central aspects of post-COVID-19 PPVOD.

Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients.

Kidney transplant (KT) recipients are at increased risk of developing severe forms of COVID-19. Little is known about the immunological mechanisms underlying disease severity in these patients receiving T-cell targeting immunosuppressive drugs. We investigated the relationship between T cell responsiveness at the beginning of the infection and the risk of subsequent progression to respiratory failure. We performed a multicentric prospective study in KT recipients with a positive RT-PCR COVID-19 test and only mild symptoms at inclusion. Blood samples were collected at baseline in a cell culture system containing T cell stimuli. We assessed T cell responsiveness by computing the ratio between the levels of Th1, Th2, Th17 and Treg cytokines produced after polyclonal stimulation and the number of blood lymphocytes. We then used an unsupervised classification approach to stratify patients into low and high T cell responders and a penalized logistic regression to evaluate the association between T cell responsiveness and progression to severe pneumonia. Forty-five patients were included. All patients who progressed to severe pneumonia (24.4%, n = 11) were low T cell responders at baseline (p = 0.01). In multivariate analysis, low T cell responsiveness at baseline was the main risk factor for subsequent progression to severe pneumonia. This study provides novel insights into the mechanisms underlying COVID-19 severity in organ transplant recipients and data of interest to clinicians managing immunosuppressive drugs in these patients.

Recurring Cystitis: How Can We Do Our Best to Help Patients Help Themselves?

Recurrent cystitis (RC) has rarely been studied; its management varies and research on a holistic approach of these patients is scarce. We attempted to characterize patients suffering from RC and investigated their current care pathways, aiming to offer customized and autonomous management. In this paper, we present a descriptive, single-center, cross-sectional study of women presenting with RC at an infectious disease (ID) clinic. A questionnaire was developed and was completed by ID physicians during patient visits. From October 2016 to January 2019, 202 women were included (mean age 59 years). Sexual intercourse, stress and diarrhoea/digestive symptoms were reported as trigger factors by 35%, 34% and 19% of patients, respectively. A majority (54%) were at risk for complications and were those more exposed to inappropriate antibiotic prescriptions. In total, 56% of women suffered from more than 10 episodes/year and 48% suffered from relapses, mainly due to E. coli. Genitourinary syndrome of menopause (GSM) was a frequent complaint (74.5% of women). Fluoroquinolones and 3rd generation cephalosporins were prescribed in 38% and 30% of women, respectively. Most women wished for non-antimicrobial approaches and autonomy. Patients require comprehensive, tailored care in order to benefit from a broader range of treatment options in compliance with recommendations.

What about using sniffin' sticks 12 items test to screen post-COVID-19 olfactory disorders?

BACKGROUND: Post-COVID-19 Olfactory impairment has a negative impact on quality of life. The Sniffin Sticks test 12 items (SST-12) can be used in quick olfactory disorders screening. Its evaluation in a post-covid-19 situation was the main objective of this work. METHODS: All patient impaired with a post-COVID olfactory loss were included while consulting to the ENT department. The clinical examination included an olfaction recovery self-assessment (VAS), a nasofibroscopy, a quality of life (QoL) assessment, the complete Sniffin' Sticks Test (SST), and the SST-12. RESULTS: Among the 54 patients included, 92% (n = 50) were correctly screened as olfactory impaired by SST-12. We report excellent correlations between SST-12 and SST (rho (52) = 0.98, p < 0.001), QoL(rho(52) = 0.33 p = 0.016), or VAS (rho(52) = 0.49, p < 0.001) assessments. CONCLUSIONS: SST-12 is a quick and reliable tool to screen large-scale population of post-COVID-19 olfactory impaired patients and could be used in a general daily clinical practice.

COVID-19 patients age, comorbidity profiles and clinical presentation related to the SARS-CoV-2 UK-variant spread in the Southeast of France.

The variant 20I/501Y.V1, associated to a higher risk of transmissibility, emerged in Nice city (Southeast of France, French Riviera) during January 2021. The pandemic has resumed late December 2020 in this area. A high incidence rate together with a fast turn-over of the main circulating variants, provided us the opportunity to analyze modifications in clinical profile and outcome traits. We performed an observational study in the University hospital of Nice from December 2020 to February 2021. We analyzed data of sequencing of SARS-CoV-2 from the sewage collector and PCR screening from all positive samples at the hospital. Then, we described the characteristics of all COVID-19 patients admitted in the emergency department (ED) (n = 1247) and those hospitalized in the infectious diseases ward or ICU (n = 232). The UK-variant was absent in this area in December, then increasingly spread in January representing 59% of the PCR screening performed mid-February. The rate of patients over 65 years admitted to the ED decreased from 63 to 50% (p = 0.001). The mean age of hospitalized patients in the infectious diseases ward decreased from 70.7 to 59.2 (p < 0.001) while the proportion of patients without comorbidity increased from 16 to 42% (p = 0.007). Spread of the UK-variant in the Southeast of France affects younger and healthier patients.

Proteinuria as a Biomarker for COVID-19 Severity.

BACKGROUND: Renal involvement in syndrome coronavirus 2 (SARS-CoV-2) infection has been retrospectively described, especially acute kidney injury (AKI). However, quantitative proteinuria assessment and its implication in coronavirus disease 2019 (COVID-19) remain unknown. METHODS: In this prospective, multicenter study in France, we collected clinical and biological data including urinary protein to creatine ratio (UPCR) in patients presenting with moderate to severe COVID-19. Clinical outcome was analyzed according to the level of UPCR. RESULTS: 42/45 patients (93.3%) had renal involvement (abnormal urinary sediment and/or AKI). Significant proteinuria occurred in 60% of patients. Urine protein electrophoresis showed tubular protein excretion in 83.8% of patients with proteinuria. Inflammatory parametersand D-dimer concentrations correlated with proteinuria level. Patients who required intensive care unit (ICU) admission had higher proteinuria (p = 0.008). On multivariate analysis, proteinuria greater than 0.3 g/g was related to a higher prevalence of ICU admission [OR = 4.72, IC95 (1.16-23.21), p = 0.03], acute respiratory distress syndrome (ARDS) [OR = 6.89, IC95 (1.41-53.01, p = 0.02)], nosocomial infections [OR = 3.75, IC95 (1.11-13.55), p = 0.03], longer inpatient hospital stay (p = 0.003). CONCLUSION: Renal involvement is common in moderate to severe SARS-CoV-2 infection. Proteinuria at baseline is an independent risk factor for increased hospitalization duration and ICU admission in patients with COVID-19.

A case of infective endocarditis caused by Arthrobacter woluwensis.

Corynebacteria are rare causative agents of infective endocarditis. This is a reported case of a destructive aorto-mitral infective endocarditis caused by Arthrobacter woluwensis. Microbial identification was achieved by 16S rRNA polymerase chain reaction on valve tissue samples. Outcome was favorable after surgical valve replacement and 4-week antibiotic treatment.

Case Report: Autoimmune Hemolysis Anemia After Dihydroartemisinin and Piperaquine for Uncomplicated Plasmodium falciparum Malaria.

Malaria is still an endemic disease in Africa, with many imported cases in Europe. The standard treatment is intravenous artesunate for severe malaria and oral artemisinin-based combination therapy (ACT) for uncomplicated malaria. Delayed hemolytic anemia (DHA) after intravenous artesunate has been extensively described, and guidelines recommend biological monitoring until 1 month after the end of the treatment. A link with an autoimmune process is still unsure. Nevertheless, cases with positive direct antiglobulin test (DAT) have been reported. Conversely, DHA is not recognized as an adverse effect of oral ACT. Previously, only few cases of DHA occurring after oral ACT without intravenous artesunate administration have been reported. We report the case of a 42-year-old man returning from Togo. He was treated with dihydroartemisinin/piperaquine combination for uncomplicated Plasmodium falciparum malaria, with low parasitemia. Nine days after the end of the treatment, the patient developed hemolytic anemia with positive DAT. Eventually, the patient recovered after corticotherapy. After excluding common causes of autoimmune hemolytic anemia, we considered that dihydroartemisinin/piperaquine treatment was involved in this side effect.

A Population Pharmacokinetic Analysis of Continuous Infusion of Cloxacillin during Staphylococcus aureus Bone and Joint Infections.

Intravenous administration of antibiotics is recommended during the early phase of methicillin-susceptible S. aureus (MSSA) bone and joint infection (BJI). We sought to compare the plasma concentrations of cloxacillin administered alternately by continuous and intermittent infusion (CI and ItI) in patients with MSSA BJI. In this prospective crossover trial, patients were randomly assigned to receive either 3 days of CI (two 75-mg/kg 12-h cloxacillin infusions per day) and then 3 days of ItI (four 37.5-mg/kg 1-h cloxacillin infusions per day) or vice versa. The drug concentration measurement was performed on day 3 of each type of administration at 1, 6, and 11 h and at 1, 2, 3, 4, and 6 h after the beginning of CI and ItI, respectively. We used the nonparametric algorithm NPAG to estimate population pharmacokinetic (PK) parameters. The final model was used to perform pharmacokinetic/pharmacodynamic (PK/PD) simulations and calculate the probabilities of target attainment (PTA) for several ItI and CI dosing regimens. We considered two PK/PD targets of time spent above the MIC for free cloxacillin concentrations (fT>MIC): 50 and 100%. Eighty-four concentrations from 11 patients were analyzed. A two-compartment model adequately described the data. ItI with q6h regimens and short 1-h infusions of 2,000 or 3,000 mg were associated with low PTA, even for the low target (50% fT>MIC) while 3-h infusions and continuous infusions (6 to 12 g/day) were associated with a PTA of >90% for an MIC up to 0.5 mg/liter. These results support the use of prolonged or continuous infusion of cloxacillin in patients with BJI.

Functional Exhaustion of Type I and II Interferons Production in Severe COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan in December 2019 and has since spread across the world. Even though the majority of patients remain completely asymptomatic, some develop severe systemic complications. In this prospective study we compared the immunological profile of 101 COVID-19 patients with either mild, moderate or severe form of the disease according to the WHO classification, as well as of 50 healthy subjects, in order to identify functional immune factors independently associated with severe forms of COVID-19. Plasma cytokine levels, and cytokine levels upon in vitro non-specific stimulation of innate and adaptive immune cells, were measured at several time points during the course of the disease. As described previously, inflammatory cytokines IL1ß, IL6, IL8, and TNFα associated with cytokine storm were significantly increased in the plasma of moderate and severe COVID-19 patients (p < 0.0001 for all cytokines). During follow-up, plasma IL6 levels decreased between the moment of admission to the hospital and at the last observation carried forward for patients with favorable outcome (p = 0.02148). After in vitro stimulation of immune cells from COVID-19 patients, reduced levels of both type I and type II interferons (IFNs) upon in vitro stimulation were correlated with increased disease severity [type I IFN (IFNα): p > 0.0001 mild vs. moderate and severe; type II IFN (IFNγ): p = 0.0002 mild vs. moderate and p < 0.0001 mild vs. severe] suggesting a functional exhaustion of IFNs production. Stimulated IFNα levels lower than 2.1 pg/ml and IFNγ levels lower than 15 IU/mL at admission to the hospital were associated with more complications during hospitalization (p = 0.0098 and p =0.0002, respectively). A low IFNγ level was also confirmed by multivariable analysis [p = 0.0349 OR = 0.98 (0.962; 0.999)] as an independent factor of complications. In vitro treatment with type IFNα restored type IFNγ secretion in COVID-19 patients while the secretion of pro-inflammatory cytokines IL6 and IL1ß remained stable or decreased, respectively. These results (a) demonstrate a functional exhaustion of both innate and adaptive immune response in severe forms of COVID-19; (b) identify IFNα and IFNγ as new potential biomarkers of severity; and (c) highlight the importance of targeting IFNs when considering COVID-19 treatment in order to re-establish a normal balance between inflammatory and Th1 effector cytokines.

Humoral and Cellular Response of Frontline Health Care Workers Infected by SARS-CoV-2 in Nice, France: A Prospective Single-Center Cohort Study.

Frontline health care workers (HCWs) have been particularly exposed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) since the start of the pandemic but the clinical features and immune responses of those infected with SARS-CoV-2 have not been well described. In a prospective single center cohort study, we enrolled 196 frontline HCWs exposed to the SARS-Cov-2 and 60 patients with moderate and severe forms of the coronavirus disease 2019 (COVID-19). Serological tests and cytokines assay were performed to analyze SARS-CoV-2-specific humoral and cellular immunity. Of the 196 HCWs tested, 15% had specific antibodies against SARS-CoV-2 and 45% of seropositive HCWs were strictly asymptomatic. However, in comparison to moderate and severe forms, HCWs with mild or asymptomatic forms of COVID-19 showed lower specific IgA and IgG peaks, consistent with their mild symptoms, and a robust immune cellular response, illustrated by a high production of type I and II interferons. Further studies are needed to evaluate whether this interferon functional immune assay, routinely applicable, can be useful in predicting the risk of severe forms of COVID-19.

Amoxicillin/clavulanic acid+aminoglycoside as empirical antibiotic treatment in severe community-acquired infections with diagnostic uncertainty.

Diagnostic uncertainty is common in the emergency room and multidrug-resistant bacteria emerge in the community setting, implying to establish the most efficient empirical antibiotic therapy (eEAT). Our aim was to identify such eEAT, considering that in case of DU with severe clinical presentation, most prescribers would propose an empiric combination (EC). The medical dashboard of our ward records prospectively 28 characteristics of each hospitalization including hospitalization motive, final diagnosis, and all antibiotics prescribed. All patients with community-acquired bacteremia (CAB) were included. DU was defined by a discrepancy between suspected diagnosis in the emergency room and final diagnosis. eEAT was defined by in vitro activity of at least one prescribed compound. Finally, independently from the dashboard, we retrospectively compared 2 CTs: amoxicillin/clavulanic acid (AMC)+gentamicin (G) and cefotaxime (3GC)+G. One thousand thirty-four patients with a final diagnosis of CAB were identified from July 2005 to June 2018, including 357 DU (35%) at baseline. eEAT (n = 553) was associated with a trend towards a lower death rate compared to inefficient therapies: 5.4 vs 10.0% (p = 0.053), and effective antibiotic reassessment was the most protective factor against an unfavorable outcome: 0.34 (0.16-0.71). Bacteria involved in case of UD were resistant to AMC+G and to 3GC+G in 8.1% and 12.8% of patients, respectively. Diagnostic uncertainty was a frequent event requiring antibiotic reassessment. As the latter was not systematically realized, the best eEAT is required and AMC+aminoglycoside should be considered.

Adherence to antibiotic guidelines for erysipelas or cellulitis is associated with a favorable outcome.

Outside areas of S. aureus strains resistant to methicillin (MRSA) in the community, no studies showed a relationship between the treatment for erysipelas or cellulitis and the outcome. We aimed to measure the impact of an internal therapeutic protocol, based on national guidelines on patients' outcome. This study was based on the dashboard of the infectious diseases department, which prospectively includes 28 parameters for all admitted patients. We included community-acquired erysipelas and cellulitis; exclusion criteria were abscesses at admission; ear, nose, throat, or dental cellulitis; pyomyositis; and length of stay ≤ 2 days. Adherence to guidelines was defined by the use of amoxicillin, amoxicillin/clavulanic acid, clindamycin, or pristinamycin, alone or in combination or successively. A poor outcome was defined by surgical procedure or intensive care requirement or death occurring after 5 days or more of antibiotic therapy. From July 2005 to June 2017, 630 cases of erysipelas or cellulitis were included. Blood cultures performed in 567 patients (90%) were positive in 39 cases (6.9%). Adherence rate to guidelines was 65% (410 cases). A poor outcome was recorded in 54 (8.5%) patients, less frequently in case of adherence to guidelines: 26/410 (6.3%) vs 28/220 (12.7%), p = 0.007. In logistic regression analysis, two risk factors were associated with a poor outcome: peripheral arterial disease, AOR 4.80 (2.20-10.49); and bacteremia, AOR 5.21 (2.31-11.76), while guideline adherence was the only modifiable protective factor, OR 0.48 (0.26-0.89). In erysipelas and cellulitis, adherence to guidelines was associated with a favorable outcome.

Factors associated with unfavorable outcome in a multicenter audit of 100 infective endocarditis.

We aimed to identify factors associated with unfavorable outcome in patients treated for infective endocarditis (IE), with a focus on departure from European guidelines. We conducted a retrospective audit of all adult patients treated for endocarditis during a 1-year period across a regional network of nine care centers in the south-east of France. Medical records were reviewed regarding patient and infection characteristics, antibiotic therapy, outcome, and compliance to the European Society of Cardiology guidelines. Antibiotic treatment appropriateness was evaluated regarding molecule, dosage, and duration, according to guidelines. Primary endpoint was the assessment of factors associated with unfavorable outcome, defined as in-hospital mortality or IE relapse at 1-year follow-up. Secondary endpoints were intensive care admission, iatrogenic events, and nosocomial infections that occurred during hospital stay. One hundred patients were included. Median age was 71 years old. Twenty-two patients died and IE relapse occurred in two patients, representing 24 patients with unfavorable outcome. Overall, antibiotic treatment was deemed appropriate in 28 cases. Thirty-three patients required intensive care, 34 iatrogenic events were found, including 19 acute kidney injuries, and 13 nosocomial infections occurred during care. Using a logistic regression, factors associated with unfavorable outcome were admission in the intensive care unit (adjusted odd ratio 7.26 [1.8-29.28]; p = 0.005), new-onset nosocomial infection (adjusted odd ratio 8.83 [1.42-54.6]; p = 0.019), and age > 71 years old (adjusted odd ratio 11.2 [2.76-46.17]; p < 0.001). Departure from guidelines was frequent but not related to unfavorable outcome in our study. Only intensive care, age, and nosocomial infections were associated with mortality and relapse. Iatrogenic events were numerous, with no impact on outcome.

Cefoxitin-based antibiotic therapy for extended-spectrum ß-lactamase-producing Enterobacteriaceae prostatitis: a prospective pilot study.

The emergence of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) infections requires re-assessment of therapeutic choices. Here we report the efficacy of cefoxitin-based antibiotic therapy for ESBL-E prostatitis. A prospective study including patients with ESBL-E prostatitis resistant to trimethoprim/sulfamethoxazole and fluoroquinolones from January 2014 to March 2016 was conducted. Cefoxitin was administered by continuous infusion for 3 weeks in the case of acute bacterial prostatitis or 6 weeks in the case of chronic bacterial prostatitis (CBP), with intravenous fosfomycin for the first 5 days. Urological investigations were performed to diagnose underlying urinary tract pathology. Clinical and microbiological efficacy were evaluated 3 months (M3) and 6 months (M6) after the end of therapy. A total of 23 patients were included in the study. The median patient age was 74 years (range 48-88 years). Of the 23 infections, 14 (61%) were CBP and 12 (52%) were healthcare-associated infections. The bacteria involved were Escherichia coli in 11 cases, Klebsiella pneumoniae in 10 cases and Klebsiella oxytoca in 2 cases. Clinical cure was observed in 19/23 patients (83%) at M3 and in 17/22 patients (77%) at M6. Urocultures were sterile in 13/23 patients (57%) at M3 and in 9/19 patients (47%) and M6. Urinary colonisation was observed in 6/19 patients (32%) with clinical cure at M3 and 5/14 patients (36%) with clinical cure at M6. No resistance to cefoxitin was detected. Surgical treatment was required for 7/23 patients (30%). In conclusion, cefoxitin-based antibiotic therapy is suitable for difficult-to-treat ESBL-E infections such as prostatitis.