Bothrops atrox and Bothrops lanceolatus Venoms In Vitro Investigation: Composition, Procoagulant Effects, Co-Factor Dependency, and Correction Using Antivenoms.

Bothrops venoms are rich in enzymes acting on platelets and coagulation. This action is dependent on two major co-factors, i.e., calcium and phospholipids, while antivenoms variably neutralize venom-related coagulopathy effects. Our aims were (i) to describe the composition of B. atrox and B. lanceolatus venoms; (ii) to study their activity on the whole blood using rotational thromboelastometry (ROTEM); (iii) to evaluate the contribution of calcium and phospholipids in their activity; and (iv) to compare the effectiveness of four antivenoms (Bothrofav™, Inoserp™ South America, Antivipmyn™ TRI, and PoliVal-ICP™) on the procoagulant activity of these two venoms. Venom composition was comparable. Both venoms exhibited hypercoagulant effects. B. lanceolatus venom was completely dependent on calcium but less dependent on phospholipids than B. atrox venom to induce in vitro coagulation. The four antivenoms neutralized the procoagulant activity of the two venoms; however, with quantitative differences. Bothrofav™ was more effective against both venoms than the three other antivenoms. The relatively similar venom-induced effects in vitro were unexpected considering the opposite clinical manifestations resulting from envenomation (i.e., systemic bleeding with B. atrox and thrombosis with B. lanceolatus). In vivo studies are warranted to better understand the pathophysiology of systemic bleeding and thrombosis associated with Bothrops bites.

Chikungunya Outbreak in Country with Multiple Vectorborne Diseases, Djibouti, 2019-2020.

During 2019-2020, a chikungunya outbreak occurred in Djibouti City, Djibouti, while dengue virus and malaria parasites were cocirculating. We used blotting paper to detect arbovirus emergence and confirm that it is a robust method for detecting and monitoring arbovirus outbreaks remotely.

Tocilizumab-treated convalescent COVID-19 patients retain the cross-neutralization potential against SARS-CoV-2 variants.

Although tocilizumab treatment in severe and critical coronavirus disease 2019 (COVID-19) patients has proven its efficacy at the clinical level, there is little evidence supporting the effect of short-term use of interleukin-6 receptor blocking therapy on the B cell sub-populations and the cross-neutralization of SARS-CoV-2 variants in convalescent COVID-19 patients. We performed immunological profiling of 69 tocilizumab-treated and non-treated convalescent COVID-19 patients in total. We observed that SARS-CoV-2-specific IgG1 titers depended on disease severity but not on tocilizumab treatment. The plasma of both treated and non-treated patients infected with the ancestral variant exhibit strong neutralizing activity against the ancestral virus and the Alpha, Beta, and Delta variants of SARS-CoV-2, whereas the Gamma and Omicron viruses were less sensitive to seroneutralization. Overall, we observed that, despite the clinical benefits of short-term tocilizumab therapy in modifying the cytokine storm associated with COVID-19 infections, there were no modifications in the robustness of B cell and IgG responses to Spike antigens.

Abbott® ID NOW™ COVID-19 rapid molecular assay versus Hologic® Panther Aptima™ SARS-CoV-2 assay in nasopharyngeal specimens: results from 1-year retrospective study in an emergency department.

We compared ID Now™ and Hologic® Panther Aptima™ for the detection of SARS-COV-2. ID Now™ showed a positive and negative percent agreement of 86.9% and 99.7% respectively. This facilitates faster clinical decision-making, along with the rapid implementation of infection control measures, and improvement of patient flow in the emergency department toward inpatient wards.

Performances, feasibility and acceptability of nasopharyngeal swab, saliva and oral-self sampling swab for the detection of severe acute respiratory syndrome coronavirus 2.

Molecular diagnosis on nasopharyngeal swabs (NPS) is the current standard for COVID-19 diagnosis, but saliva may be an alternative specimen to facilitate access to diagnosis. We compared analytic performances, feasibility and acceptability of NPS, saliva, and oral-self sampling swab for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A prospective, multicenter study was conducted in military hospitals in France among adult outpatients attending COVID-19 diagnosis centers or hospitalized patients. For each patient, all samples were obtained and analyzed simultaneously with RT-PCR or transcription-mediated amplification method. Clinical signs, feasibility, and acceptability for each type of sample were collected. A total of 1220 patients were included, corresponding to 1205 NPS and saliva and 771 OS. Compared to NPS, the sensitivity, specificity, and kappa coefficient for tests performed on saliva were 87.8% (95% CI 83.3-92.3), 97.1% (95% CI 96.1-98.1), and 0.84 (95% CI 0.80-0.88). Analytical performances were better in symptomatic patients. Ct values were significantly lower in NPS than saliva. For OS, sensitivity was estimated to be 61.1% (95% CI 52.7-69.4) and Kappa coefficient to be 0.69 (95% CI 0.62-0.76). OS was the technique preferred by the patients (44.3%) before saliva (42.4%) and NPS (13.4%). Instructions were perceived as simple by patients (> 90%) for saliva and OS. Finally, the painful nature was estimated to be 0.9 for OS, on a scale from 0 to 10, and to be 5.3 for NPS. Performances of OS are not sufficient. Saliva is an acceptable alternative to NPS for symptomatic patient but the process required additional steps to fluidize the sample.

Salmonella enterica serovar enteritidis peritonitis with spontaneous intestinal perforation in an immunocompetent patient.

Few data reported non-typhoidal Salmonella peritonitis in immunocompromised patients. We reported the case of a man without immunosuppression or predisposing factor, who developed Salmonella enterica serovar Enteritidis peritonitis with spontaneous intestinal perforation. After emergent surgery, the patient was transferred to intensive care unit (ICU) because of respiratory, renal and haemodynamic failures. When S. enterica serovar Enteritidis was identified, antibiotics were de-escalated for ceftriaxone and metronidazole for 5 days. No immunosuppression was found. Evolution was favourable, and the patient has been discharged from the ICU on day 8. The originality of this case arises from a perforation peritonitis secondary to S. enterica without any immunosuppression. In absence of non-Typhi Salmonella data, we treated this patient as a typhoid perforation: surgical treatment, antibiotic association and supportive care.

Novel patterns in the molecular epidemiology of KPC-producing Klebsiella pneumoniae in Tucumán, Argentina.

BACKGROUND: In Argentina, there has been an abrupt increase in KPC-2-producing Klebsiella pneumoniae (K. pneumoniae). Tucumán is a multi-border area, so the rapid dissemination of carbapenem-resistant K. pneumoniae is a clinically relevant problem for the region. OBJECTIVES: This study aimed to investigate the epidemiological and molecular patterns of KPC-producing K. pneumoniae clinical isolates collected from different hospitals in Tucumán. METHODS: Carbapenem-resistant K. pneumoniae strains were sequentially and uniquely collected during two time periods. Antibiotic susceptibility was determined by the automated Vitex 2® system and using the standard agar dilution test. Multilocus sequence typing and pulsed-field electrophoresis were used for epidemiological analysis. The genetic structures around blaKPC and the encoding genes of extended-spectrum ß-lactamases were detected by polymerase chain reaction and sequencing. Plasmids were analysed by conjugation and using the plasmid relaxase gene-typing method. RESULTS: All 37 isolates were multidrug resistant, and theblaKPC-2 gene was confirmed in all of them. In 17 isolates (45.9%), the blaCTX-M-2 gene was also amplified, as well as blaSHV-2 in five isolates (13.5%) and blaCTX-M-2/blaSHV-2 in four isolates (10.8%). The molecular epidemiology of the blaKPC-2 gene has resulted in it being associated with an IncL/M transferable plasmid disseminating in various sequence types (STs) (ST17, ST556, ST342, ST147, ST461, ST65, ST15 and ST70), and in a new genetic environment with a 764-bp deletion in the ISKpn7-blaKPC region. CONCLUSIONS: These findings contribute to the understanding of the great diversity of the blaKPC-2-carrying genetic platforms.

Molecular epidemiological of extended-spectrum ß-lactamase producing Escherichia coli isolated in Djibouti.

INTRODUCTION: While the molecular epidemiology of extended-spectrum-b-lactamase (ESBL)-producing E. coli is well known in Europe due to effective surveillance networks and substantial literature, data for Africa are less available, especially in Djibouti. METHODOLOGY: We studied 31 isolates of ESBL-producing E. coli from Djibouti and compared these molecular results with data available in Africa. RESULTS: Susceptibility rates were 3.2% for ceftazidim, 48.4% for piperacillin-tazobactam, 90.3% for amikacine and 16.1% for ofloxacin. No isolate showed resistance to carbapenems or colistin. 30 E. coli (96.8%) were positive to blaCTX-M-15, 1 (3.2%) to blaCTX-M-14  and 10 (32.3%) to narrow-broad-spectrum blaTEM. No blaSHV were detected. Fluoroquinolone resistance analysis showed that 30 ofloxacin-resistant E. coli had the mutation Ser-83->Leu on the gyrA gene. 24 E. coli (77.4%) harboured the plasmid-borne aac(6 ')-Ib-cr gene. No E. coli carried the genes qnrA, qnrB and qepA. 10 isolates (32.3%) belonging to the ST131 clone. The plasmid incompatibility group most widely represented in our collection was IncFIA/IB/II. CONCLUSIONS: There is no major difference with African epidemiology. In particular, we notice the international diffusion of specific clonal group ST131.

Prevalence and risk factors for Extended-Spectrum Beta-Lactamase-producing- Enterobacteriaceae in French military and civilian travelers: A cross-sectional analysis.

BACKGROUND: International travel is a risk factor for colonization with Extended-Spectrum Beta-Lactamase-producing- Enterobacteriaceae (ESBL-E). We describe the prevalence of and risk-factors for ESBL-E colonization in civilian and military travelers. METHODS: Patients hospitalized in the infectious diseases department of Bégin Military Hospital (France) from May 2012 to November 2015, who had traveled abroad over the past two months, were screened for intestinal colonization with ESBL-E. RESULTS: Forty-one out of 166 travelers (24.7%) had ESBL-E colonization, predominantly Escherichia coli. The risk factors for ESBL-E colonization in the univariate analysis were a treatment with any antibiotic in the last two months (OR 4.19, 95% CI 1.91-9.16) or with a beta-lactam in the same period (OR 3.35, 95% CI 1.44-7.82), and an hospitalization in the last two months (OR 3.96, 95% CI 1.91-9.16). The military status, military mission or military accommodation were not associated with an increased risk of ESBL-E colonization. In the multivariate analysis, a treatment with any antibiotic in the last two months was significantly associated with ESBL-E colonization (OR 6.71, 95% CI 3.36-19.08). CONCLUSION: Antibiotic treatment in the two previous months is strongly predictive of ESBL-E colonization in international travelers, while the military status and its specific living conditions are not.

Thromboelastographic study of the snakebite-related coagulopathy in Djibouti.

: Hemostasis disorders are one of the major clinical conditions of snakebites and are because of mechanisms which may disrupt vessels, platelets, clotting factors and fibrinolysis. Thromboelastography (TEG) could help to understand these effects in the clinical practice. A retrospective study reports a series of patients presenting a snakebite-related coagulopathy, treated with antivenom and monitored with conventional tests and TEG in a French military treatment facility (Republic of Djibouti, East Africa) between August 2011 and September 2013. Conventional coagulation assays (platelets, prothrombin time, activated partial thromboplastin time, fibrinogen) and TEG measurements were taken on arrival and at various times during the first 72 h of hospitalization, at the discretion of the physician. The study included 14 patients (median age 28 years). Bleedings were present in five patients. All patients received antivenom. A coagulopathy was present in all patients and was detected by both conventional assays and TEG. None exhibited thrombocytopenia. Prothrombin time and fibrinogen remained abnormal for most of patients during the first 72 h. The TEG profiles of 11 patients (79%) showed incoagulability at admission (R-time > 60 min). TEG distinguished 10 patients with a generalized clotting factor deficiency and 4 patients with an isolated fibrinogen deficiency after an initial profile of incoagulability. Hyperfibrinolysis was evident for 12 patients (86%) after Hour 6. Snake envenomations in Djibouti involve a consumption coagulopathy in conjunction with delayed hyperfibrinolysis. TEG could improve medical management of the condition and assessment of additional therapeutics associated with the antivenom.

Clinical isolates of Escherichia coli solely resistant to mecillinam: prevalence and epidemiology.

In routine susceptibility testing of Gram-negative bacteria, a particular resistance phenotype was observed: an Escherichia coli isolate from a urine sample exhibited resistance solely to mecillinam (MEC) but was fully susceptible to other ß-lactam antibiotics (MEC-R-BL-S). The objectives as this study were to determine the prevalence of this phenotype and to describe the phenotype, molecular epidemiology and genetic background. Between 1 January 2014 and 31 January 2016, MEC-R-BL-S E. coli isolates from urine were collected and genes previously reported as mostly involved in MEC resistance were analysed. The genetic relatedness among isolates was investigated by repetitive element sequence-based PCR (rep-PCR) and multilocus sequence typing (MLST). Ten MEC-R-BL-S isolates were collected, accounting for 0.4% (10/2547) of all E. coli obtained from urine samples, 0.9% (10/1135) of ampicillin-susceptible E. coli isolates and 9.6% (10/104) of MEC-R E. coli isolates. The isolates appeared as small colonies with round morphology and had impaired fitness. The isolates were not clonal and belonged to various extraintestinal or commensal E. coli phylogroups. Mutations in the cysB gene were evidenced in all clinical isolates. In conclusion, microbiologists should be aware of these isolates with a particular susceptibility phenotype, which is not due to error in disk diffusion but is a real non-enzymatic antibiotic resistance pattern.

Mycoplasma genitalium: a mycoplasma still underestimated.

Three men referred to the emergency department with suspected sexually transmitted infection like urethritis. After collection of several clinical specimens, they are sent home with a probabilistic treatment. Mycoplasma genitalium research is performed in first line, as Neisseria gonorrhoeae and Chlamydia trachomatis, and comes back positive. Patients are recalled in order to evaluate probabilistic treatment efficiency. M. genitalium, still underestimated because of its recent discovery, is responsible for 10 to 35% of non gonococcal acute and chronical urethritis. Its research is performed by PCR from urogenital specimens like genital swab or first void urine. Until recently, M. genitalium treatment included azithromycin 1g, antibiotic recommended in association with ceftriaxone in the probabilistic treatment of sexually transmitted infections. However, since the discovery of therapeutic failures and the emergence of resistance to azithromycin monodose, azithromycin in extended treatment (500 mg on the first day followed by 250 mg daily during 4 days) is now recommended as first-line agent when M. genitalium is well identified. A control by PCR is expected 4 or 5 weeks after treatment.

Peripherally Inserted Central Catheter-Related Infections in a Cohort of Hospitalized Adult Patients.

PURPOSE: To determine the incidence and the risks factors of peripherally inserted central catheter (PICC)-related infectious complications. MATERIALS AND METHODS: Medical charts of every in-patient that underwent a PICC insertion in our hospital between January 2010 and October 2013 were reviewed. All PICC-related infections were recorded and categorized as catheter-related bloodstream infections (CR-BSI), exit-site infections, and septic thrombophlebitis. RESULTS: Nine hundred and twenty-three PICCs were placed in 644 unique patients, mostly male (68.3%) with a median age of 58 years. 31 (3.4%) PICC-related infections occurred during the study period corresponding to an infection rate of 1.64 per 1000 catheter-days. We observed 27 (87.1%) CR-BSI, corresponding to a rate of 1.43 per 1000 catheter-days, 3 (9.7%) septic thrombophlebitis, and 1 (3.2%) exit-site infection. Multivariate logistic regression analysis showed a higher PICC-related infection rate with chemotherapy (odds ratio (OR) 7.2-confidence interval (CI) 95% [1.77-29.5]), auto/allograft (OR 5.9-CI 95% [1.2-29.2]), and anti-coagulant therapy (OR 2.2-95% [1.4-12]). CONCLUSION: Chemotherapy, auto/allograft, and anti-coagulant therapy are associated with an increased risk of developing PICC-related infections. CLINICAL ADVANCE: Chemotherapy, auto/allograft, and anti-coagulant therapy are important predictors of PICC-associated infections. A careful assessment of these risk factors may be important for future success in preventing PICC-related infections.