High Frequency of Specific Polysaccharide Antibody Deficiency in Adults With Unexplained, Recurrent and/or Severe Infections With Encapsulated Bacteria.

BACKGROUND: Primary immunodeficiencies (PIDs) in adults are mainly revealed by recurrent and/or severe bacterial infections. The objective of this study was to evaluate a systematic research strategy of PIDs in adults with unexplained bacterial infections, with a special focus on specific polysaccharide antibody deficiency (SPAD). METHODS: In this prospective multicenter study, inclusion criteria were recurrent benign upper and lower respiratory tract infections (RTIs) for at least two years (group 1), at least one upper or lower RTI requiring hospitalization (group 2), and/or at least one invasive infection documented with encapsulated bacteria (group 3). Main exclusion criteria were all local and general conditions that could explain infections. If no PID diagnosis was made, response to polysaccharide antigens was assessed using a pneumococcal polysaccharide vaccine. RESULTS: From March 2015 to March 2020, 118 patients were included (37 males, median age of 41 years): 73, 17, and 28 in groups 1, 2, and 3, respectively. Forty-seven PIDs were diagnosed, giving an estimated frequency of 39.8% (95% confidence interval [CI] [30.4, 48.8]). SPAD was the most frequent diagnosis by far (n = 37/47, 78.7%), and was made in 23, 5, and 9 patients from groups 1 to 3, respectively. All SPAD patients received conjugate vaccines and, according to their infectious history, were on surveillance or treated with preventive antibiotics (n = 6) and/or with immunoglobulins replacement therapy (n = 10), the latter being dramatically efficient in all cases. CONCLUSIONS: Considering its high prevalence among adults with unexplained recurrent and/or severe bacterial infections, SPAD should be screened in those patients. CLINICAL TRIALS REGISTRATION: NCT02972281.

An unusual case of native aortic endocarditis due to Corynebacterium pseudodiphtheriticum.

Corynebacterium pseudodiphtheriticum, a Gram-positive rod belonging the oropharynx microbiota, is usually described in pulmonary infections, especially in immunocompromised patients. This paper describes a rare case of native aortic infectious endocarditis (IE) and reviews the literature on similar cases. A 62-year-old man with rheumatic fever since childhood was hospitalized for surgical treatment of a febrile IE due to C. diphtheriticum with a large vegetation (15.8 X 8.3 mm). MALDI-TOF-MS from strain isolated in positive blood cultures identified C. pseudodiphtheriticum (2.34), and 16S rRNA sequencing from the valve sample confirmed the identification. The summary of 25 cases shows that the outcome of an IE due to C. pseudodiphtheriticum is bad. The review of the literature shows that this agent found in blood cultures in a cardiovascular context deserves to be explored meticulously because an unfavorable prognosis is frequent.

Comparison of time-to-positivity between two blood culture systems: a detailed analysis down to the genus-level.

A recently developed, automated blood culture system and medium improve the time-to-positivity (TTP) for bacteremia. However, there have thus far been no genus-level analyses using this novel system. We evaluated and compared the changes in blood culture TTP between two systems: BacT/Alert 3D with a blood culture medium containing activated charcoal versus the more recent BacT/Alert Virtuo with a blood culture medium containing polymeric beads. This before-and-after study included blood cultures collected between July 2010 and April 2014 (3D, activated charcoal) and between July 2015 and April 2018 (Virtuo, polymeric beads). A total of 554,732 blood cultures were included, 267,935 (48.30%) during the first period and 286,797 (51.70%) during the second period. Overall, 55,611 (10.02%) tested positive for at least one microorganism. The incubation of the blood culture medium in the Virtuo system was associated with reduced TTP for the most prevalent bacteria, those representing 91.72% (n=51,006) of all the positive blood cultures. The median TTP was reduced by 0.99 h for Staphylococcus, Enterococcus, Streptococcus, Pseudomonadales, and most of the genera within the order Enterobacterales (except the family Morganellaceae). However, strictly anaerobic bacteria belonging to the genus Bacteroides, representing 0.85% (n=474) of all positive blood cultures, were detected 4.53 h later using the Virtuo system. Virtuo was associated with a shorter TTP for most bacteria, but this improvement was heterogeneous to the genus level.

Evaluation of the new BL-RED (ß-Lactamase Rapid Electrochemical Detection) test in positive blood culture broths.

The rapid detection of extended-spectrum ß-lactamase Enterobacterales (ESBL-E) in a positive blood culture is important in order to initiate an appropriate antibiotic therapy and thus decrease mortality. We evaluated the new BL-RED (ß-Lactamase Rapid Electrochemical Detection) test in 100 positive blood culture broths to detect (in ten minutes) the presence or absence of ESBL-E. The BL-RED test appears to be an easy, rapid and reliable test to detect the presence of ESBL directly in Gram negative bacilli-positive blood culture broths, with good performances (sensibility =97.3%, specificity =90.5%, predictive positive value =85.7% and predictive negative value =98.3%). This test could be useful for therapeutic decisions and adjustments of sepsis empirical antibiotic therapy, particularly in wards where the ecology is unfavorable, such as in intensive care units.

Panton-Valentine Leukocidin-Secreting Staphylococcus aureus Pneumonia Complicating COVID-19.

Necrotizing pneumonia induced by Panton-Valentine leukocidin-secreting Staphylococcus aureus is a rare but life-threatening infection that has been described in patients after they had influenza. We report a fatal case of this superinfection in a young adult who had coronavirus disease.

Yersinia enterocolitica biotype 1B case report: an unusual pathogen in an osteoarticular infection on device.

BACKGROUND: Yersinia enterocolitica is an aero-anaerobic Gram-negative coccobacilli of the Enterobacteriaceae family, rarely reported in osteoarticular infection. CASE PRESENTATION: This report case described a rare septic osteoarticular infection on device due to Yersinia enterocolitica biotype 1B. A purulent fistula appeared after osteosynthesis with plate performed abroad 27 days prior to the presentation for a distal femoral fracture. The treatment consisted of surgical irrigation and washing of the femoral plate and a bitherapy by levoflaxacine and ceftriaxone during 3 months. CONCLUSION: Y. enterocolitica biotype 1B is extremely rare in France. Moreover, the strain implicated in this european case is extremely close from the USA reference strain (with only 2 SNP difference) described in a septicemia in Ohio. The extreme proximity of the strains underlines the need for a sustained surveillance of the spread of this pathogen in France.

Ceftobiprole: a potential empirical post-operative monotherapy in prosthetic joint infections.

BACKGROUND: This study aimed to evaluate in vitro susceptibility to ceftobiprole of clinical strains identified from prosthetic joint infections (PJIs) compared to that of the associations currently recommended for post-operative empirical antibiotic therapy (PEAT) (vancomycin with either cefepime, third-generation cephalosporin or piperacillin-tazobactam). METHODS: We performed a 1-year retrospective study on all the surgical procedures performed in our hospital for PJI. Susceptibility profiles of all the strains cultured from surgical samples were reviewed to compare ceftobiprole to current used associations. RESULTS: During the study period (from January 2018 to December 2018), we identified 106 patients managed for PJI and a total of 216 surgical interventions. One hundred-fifty strains were identified from intraoperative samples, excluding redundant strains. Staphylococcus spp. represented 52.7% of all strains and Enterobacteriales 13.3%. Twenty-three patients had polymicrobial infection (22%). Among 149 surgical procedures with positive culture results, ceftobiprole covered the bacterial strains in 138 (92.6%) cases. In comparison, this percentage was 94.6% for vancomycin plus cefepime (p = 0.64), 92.6% for vancomycin plus a third-generation cephalosporin in 138 cases (p = 1) and 94.6% for vancomycin plus piperacillin-tazobactam) (p = 0.64). CONCLUSION: Based on antimicrobial susceptibility testing, our results suggest that ceftobiprole could be an interesting option for PEAT in PJIs, allowing the use of a single agent.

Sneathia amnii, an unusual pathogen in spondylitis: A case report.

Sneathia amnii is an opportunistic pathogen of the female reproductive tract that has been reported to cause infections during pregnancy and in the post-partum period. Infections outside the reproductive tract have rarely been described. We report the case of a spondylitis due to S. amnii in a 72-year old woman, successfully treated after seven weeks of antimicrobial therapy. Growth of this pathogen guided our diagnosis towards a gynecological pathology; we discovered an endometrium adenocarcinoma. This case emphasizes the need for adequate incubation of discal biopsies, using aerobic and anaerobic enrichment broth with prolonged incubation.

Clinical relevance of Clostridium bacteremia: An 8-year retrospective study.

Clostridium spp. are recovered from 25% of the blood culture positive with anaerobes. However, the clinical relevance of Clostridium bacteremia has been controverted in the literature, particularly for C. perfringens. We aimed to evaluate the clinical relevance of Clostridium bacteremia, either due to C. perfringens or other Clostridium species, and to identify the risk factors of mortality in these patients. A retrospective cohort study was conducted from January 2010 to April 2018. All the patients with at least one blood culture positive with any Clostridium species were included. Eighty-one patients with a least one blood culture positive with any Clostridium species were included. Seventy patients (86.4%) fulfilled the criteria for clinically relevant bacteremia. Bacteremia due to C. perfringens tended to be less clinically relevant than other Clostridium species but this was not statistically significant (76% vs 91.2%, P = 0.09). In case of clinically relevant bacteremia, the 30-day mortality rate was 31.4%. In multivariate analysis, adequate empiric antimicrobial therapy was significantly associated with survival (P = 0.03). In conclusion, bacteremia due to C. perfringens or other Clostridium species is usually clinically relevant. This finding was also supported by an improved survival at 30 days when adequate empiric antimicrobial therapy was administered.

Pneumonia-Specific Escherichia coli with Distinct Phylogenetic and Virulence Profiles, France, 2012-2014.

In a prospective, nationwide study in France of Escherichia coli responsible for pneumonia in patients receiving mechanical ventilation, we determined E. coli antimicrobial susceptibility, phylotype, O-type, and virulence factor gene content. We compared 260 isolates with those of 2 published collections containing commensal and bacteremia isolates. The preponderant phylogenetic group was B2 (59.6%), and the predominant sequence type complex (STc) was STc73. STc127 and STc141 were overrepresented and STc95 underrepresented in pneumonia isolates compared with bacteremia isolates. Pneumonia isolates carried higher proportions of virulence genes sfa/foc, papGIII, hlyC, cnf1, and iroN compared with bacteremia isolates. Virulence factor gene content and antimicrobial drug resistance were higher in pneumonia than in commensal isolates. Genomic and phylogenetic characteristics of E. coli pneumonia isolates from critically ill patients indicate that they belong to the extraintestinal pathogenic E. coli pathovar but have distinguishable lung-specific traits.

Is the Unyvero i60 ITI multiplex PCR system a promising test in the diagnosis of infective endocarditis from heart valves?

The aim of this study was to evaluate the new commercial Unyvero i60 ITI multiplex PCR system (Curetis, Holzgerlingen, Germany) on native cardiac valves in comparison with made in-house 16S rRNA PCR amplification (91E/13BS primers) and conventional microbiological techniques. Forty-four patients (30 men, 14 women) with suspected infective endocarditis (IE) were included in this evaluation corresponding to 30 aortic valves and 14 mitral valves. IE was definite for 40 patients using the modified Duke criteria. 16S rRNA PCR amplification was successful in 22 patients (55%). The Unyvero i60 ITI cartridge yielded a positive result in 16 patients (40%). Among the 40 cases, the etiological agent was not included in the panel of Unyvero i60 ITI cartridge for 14 cases. Moreover, for S. aureus, the Unyvero i60 ITI cartridge quickly yielded the susceptibility to meticillin. The result of the experiment was available after 5 hours whereas 16S rRNA PCR amplification-sequencing needs 14 hours of manipulation. If the manufacturer incorporates new targets able to detect more endocarditis agents such as viridans streptococci, the Unyvero i60 ITI cartridge may be a promising and easy-to-use test.

Fungal and Bacterial Diversity of Airway Microbiota in Adults with Cystic Fibrosis: Concordance Between Conventional Methods and Ultra-Deep Sequencing, and Their Practical use in the Clinical Laboratory.

Given the complexity of the airway microbiota in the respiratory tract of cystic fibrosis (CF) patients, it seems crucial to compile the most exhaustive and exact list of the microbial communities inhabiting CF airways. The aim of the present study was to compare the bacterial and fungal diversity of sputa from adult CF patients during non-exacerbation period by culture-based and molecular methods, and ultra-deep-sequencing (UDS). Sputum samples from four CF patients were cultured and analysed by DNA extractions followed by terminal restriction fragment length polymorphism analysis through resolution of bacterial ribosomal gene (rDNA) fragments, and cloning plus sequencing of part of fungal rRNA genes. These approaches were compared with UDS method targeting 16S rDNA gene and the internal transcribed spacer (ITS) 2 region of rDNA. A total of 27 bacterial and 18 fungal genera were detected from the four patients. Five (18%) and 3 (16%) genera were detected by culture for bacteria and fungi, respectively, 9 (33%) and 3 (16%) by first generation sequencing (FGS) methods, and 26 (96%) and 18 (100%) by UDS. The mean number of genera detected by UDS per patient was statistically higher than by culture or FGS methods. Patients with severe airway disease as assessed by standard spirometry exhibited a reduced fungal and bacterial diversity. UDS approach evaluates more extensively the diversity of fungal and bacterial flora compared with cultures. However, it currently remains difficult to routinely use UDS mainly because of the lack of standardization, and the current cost of this method.

Specific Polysaccharide Antibody Deficiency Revealed by Severe Bacterial Infections in Adulthood: A Report on 11 Cases.

We report on 11 cases of specific polysaccharide antibody deficiency (SPAD) revealed in adulthood by severe infections with encapsulated bacteria. Given that immunoglobulin replacement therapy can effectively prevent the recurrence of bacterial infections in this context, SPAD should be considered once other antibody deficiencies have been ruled out.

Familial Transmission of emm12 Group A Streptococcus.

Incidence and severity of invasive group A Streptococcus infections are of increasing concern in France and worldwide. The risk for secondary infection of close contacts is known but rarely described. We report a case of intrafamilial and life-threatening transmission of emm12 group A Streptococcus.

Fidaxomicin for treatment of Clostridium difficile infection in clinical practice: a prospective cohort study in a French University Hospital.

PURPOSE: Two randomized controlled trials (RCTs) showed the non-inferiority of fidaxomicin compared with vancomycin for Clostridium difficile infection (CDI) treatment and its superiority regarding recurrence rate. The aim of this study was to evaluate fidaxomicin's efficacy in clinical practice. METHODS: This single-center prospective cohort study included hospitalized patients treated with fidaxomicin for CDI. Demographic, clinical and biological data were collected. Primary outcome was efficacy of fidaxomicin (clinical cure, recurrence and global cure) at 10 weeks. Secondary outcome was efficacy among different subgroups. RESULTS: Ninety-nine patients were included: 42 severe CDI, 16 complicated CDI and 41 recurrent CDI. Rates of clinical cure, recurrence and global cure were 87, 15 and 59%, respectively. Subgroup analysis showed a higher recurrence rate for patients with recurrent CDI compared with first episode (8 vs. 26%; p = 0.04). Binary toxin was associated with severe/complicated CDI (80 vs. 50%; p < 0.01) and recurrence (32 vs. 7%; p < 0.01). Fidaxomicin was used as a first line for 83% of the patients with recurrence and for only 52% of first episodes even though 86% had recurrence's risk factors. CONCLUSION: Compared with RCTs, fidaxomicin in real world is used for patients with more severe and recurrent CDI, but clinical cure and recurrence rates were similar. Comparative studies are needed in these specific subgroups. Our data also illustrate clinicians' difficulty to define a "patient at risk for recurrence" among the first episodes. Finally, we showed that binary toxin could be important in the screening for severity and recurrence risks.