Inoculum effect of Enterobacterales co-expressing OXA-48 and CTX-M on the susceptibility to ceftazidime/avibactam and meropenem.

BACKGROUND: The treatment of infections caused by OXA-48/CTX-M-coproducing Enterobacterales may be based on new beta-lactam/beta-lactamase inhibitors, such as ceftazidime/avibactam (CZA), or on high dose of meropenem (MER). However, bacterial density at the infection site may vary widely, and the inoculum effect of such antimicrobial strategies has never been specifically investigated. To determine if CZA or MER susceptibilities are impacted by high inocula of Enterobacterales co-expressing both enzymes: OXA-48 like and CTX-M. METHODS: Determination of an inoculum effect was performed with a standard inoculum of 108 CFU/mL (0.5 McFarland) as recommended by EUCAST guidelines and compared to a twofold increase as well as a tenfold increase (1 McFarland and 5 McFarland respectively). RESULTS: Thirty-nine isolates of ceftazidime-resistant Enterobacterales were included of which 27 (70%) co-expressed OXA-48 + CTX-M-15, 6 (15%) OXA-48 + CTX-M-14, and 6 (15%) OXA-181 + CTX-M-15. The susceptibility to the CZA combination was preserved whatever the inoculum used. Regarding MER, 24 (61.5%) of the isolates were susceptible to MER with the standard inoculum, 19 (48.7%) with a twofold increase, and only 15 (38.5%) with a tenfold increase. CONCLUSION: We showed that in vitro inoculum effect was observed with meropenem but not with CZA for OXA-48- combined with CTX-M-producing Enterobacterales.

Suction drainage fluid culture during septic orthopaedic surgery, a retrospective study.

We evaluated the usefulness of suction drainage fluid culture after septic orthopaedic surgery to predict early surgical reintervention. We conducted a retrospective observational study, at the Groupe Hospitalier Paris Saint-Joseph between 2014 and 2019. All the patients undergoing septic orthopaedic surgery, with perioperative samples and a postoperative suction drainage device, were enrolled. We compared the group with positive or negative postoperative drainage fluid cultures, respectively, on surgical outcome. We included 246 patients. The drainage fluid culture was positive in 42.3% of the cases. Early surgical reintervention concerned 14.6% of the cases (n = 36), including 61.1% of patients with positive drainage fluid culture (n = 22/36). The risk factors associated with positive drainage fluid cultures were the debridement of the infected site (without orthopaedic device removal), an infection located at the spine, perioperative positive cultures to Staphylococcus aureus. The complete change of the orthopaedic device, and coagulase-negative staphylococci on the preoperative samples, was associated with negative drainage fluid cultures. Positive drainage fluid culture was predictive of early surgical reintervention, and coagulase-negative staphylococci in the preoperative samples and knee infection were predictive of surgical success. Postoperative drainage fluid cultures were predictive of early surgical reintervention. Randomized multicentric studies should be further conducted.

Impact of therapeutic drug monitoring of antibiotics in the management of infective endocarditis.

Treatment of infective endocarditis (IE) is based on high doses of antibiotics with a prolonged duration. Therapeutic drug monitoring (TDM) allows antibiotic prescription optimization and leads to a personalized medicine, but no study evaluates its interest in the management of IE. We conducted a retrospective, bicentric, descriptive study, from January 2007 to December 2019. We included patients cared for IE, defined according to Duke's criteria, for whom a TDM was requested. Clinical and microbiological data were collected after patients' charts review. We considered a trough or steady-state concentration target of 20 to 50 mg/L. We included 322 IE episodes, corresponding to 306 patients, with 78.6% (253/326) were considered definite according to Duke's criteria. Native valves were involved in 60.5% (185/306) with aortic valve in 46.6% (150/322) and mitral in 36.3% (117/322). Echocardiography was positive in 76.7% (247/322) of cases. After TDM, a dosage modification was performed in 51.5% (166/322) (decrease in 84.3% (140/166)). After initial dosage, 46.3% (82/177) and 92.8% (52/56) were considered overdosed, when amoxicillin and cloxacillin were used, respectively. The length of hospital stay was higher for patient overdosed (25 days versus 20 days (p = 0.04)), and altered creatinine clearance was associated with overdosage (p = 0.01). Our study suggests that the use of current guidelines probably leads to unnecessarily high concentrations in most patients. TDM benefits predominate in patients with altered renal function, but probably limit adverse effects related to overdosing in most patients.

Epidemiology of symptomatic infective anoproctitis in a population of men having sex with men (MSM).

PURPOSE: Anoproctitis due to Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are Sexual Transmitted Infections (STIs) reported in MSM population. This study describes clinical and microbiological epidemiology of infective anoproctitis in MSM population. METHODS: All patients with symptomatic anoproctitis consulting at the proctology Institute of Saint-Joseph's Hospital, Paris, were included. Detection of CT/NG was performed by PCR GeneXpertR and other STIs pathogens Mycoplasma sp., HSV, CMV and T. pallidum were detected by multiplex PCR Allplex (mPCR). RESULTS: Symptoms most frequently reported were pain, rectal bleeding and purulent flow in 66%, 52% and 49% of cases, respectively. On the 311 rectal samples collected, 171 (55.2%) were positive to CT/NG. Among the 194 used for mPCR, 148 were positive to STIs pathogens (76.2%) including 106 samples (71.6%) positive in coinfections. Among NG infections, 22.6% of the strains were resistant to azithromycin and 26.8% to tetracyclines. CONCLUSIONS: Anorectal infections in this MSM population showed a high prevalence of not only CT/NG but also other pathogens involved in STIs. The high level of coinfections confirms the requirement of accurate PCR tests to improve diagnosis. This study describing increasing antibiotic resistances for NG strains confirms the updating of international guidelines on antibiotic treatments recommendations.

Emergence of Ceftriaxone Resistance during a Case of Pneumococcal Meningitis with Fatal Evolution.

We report a case of a 62-year-old man treated for Streptococcus pneumoniae meningitis by ceftriaxone and dexamethasone. After neurological improvement, neurological degradation by vasculitis occurred, despite effective concentrations of ceftriaxone in the serum and cerebrospinal fluid (CSF). S. pneumoniae with increased MICs to third-generation-cephalosporins (3GC) was isolated from the ventricular fluid 10 days after the isolation of the first strain. Isolate analysis showed that a mutation in the penicillin-binding protein 2X (PBP2X) has occurred under treatment.

Implementation of Alere i Influenza A & B point of care test for the diagnosis of influenza in an ED.

STUDY OBJECTIVE: This study aimed to evaluate the impact of implementing rapid point-of-care testing (POCT) with the Alere i Influenza A & B in an emergency department (ED) during an influenza epidemic. METHODS: Direct nasal swabs were prospectively collected following the physical examination of patients aged >18years who presented to the ED of a tertiary hospital in France with influenza-like illness (ILI) symptoms (N=301) between February 1st and March 31st, 2016, which coincided with an influenza epidemic. Laboratory-based testing (standard of care) was used to obtain a diagnosis in February 2016 (pre-POCT cohort) and positive results were confirmed using polymerase chain reaction. The primary endpoint was patient time in the ED. RESULTS: A total of 169 and 132 patients participated in the pre-POCT phase and POCT phase respectively. A significantly higher proportion of patients received a positive diagnosis in the POCT cohort compared with the pre-POCT cohort (31% versus 5.3%, P<0.01). Mean time spent in the ED and hospitalization rate were significantly lower in the POCT cohort (6.06h versus 4.15h, P=0.03, and 44.4% versus 9.7%, P=0.02, respectively). Despite similar rates in the prescription of antibiotics and antiviral therapies, the proportion of patients who were referred for additional tests was significantly lower in the POCT cohort (78.1% versus 62.1%, P=0.003, and 80.5% versus 63.6%, P=0.01, respectively). CONCLUSIONS: The Alere i Influenza A & B POCT reduced the length of stay in ED, the hospitalization rates, and the number of additional diagnostic tests compared with standard of care testing.

Infections caused by Tissierella praeacuta: A report of two cases and literature review.

Herein we report two cases of infections caused by Tissierella praeacuta and a review of the literature. The first case was a septic pseudarthrosis of the left femur after multiple fractures. Two per-operative samples were positive with T. praeacuta. The patient was successfully treated by piperacillin - tazobactam and metronidazole. The second case was a bacteremia in a patient suffering from pyonephrosis and a hepatic abscess. The treatment was meropenem. No relapses were observed in both cases. Identification of the strains using MALDI-TOF coupled to mass spectrometry (MS) (Beckman coulter, France) was inconclusive in the two cases. Identification by 16S rRNA sequencing was then performed. This bacterium was susceptible to beta-lactams, chloramphenicol, rifampicine and metronidazole.

Spondylodiscitis due to anaerobic bacteria about a case of Parvimonas micra infection.

Parvimonas micra is a rare isolate in clinical specimens. We report a case of spondylodiscitis caused by P. micra, a rarely reported Gram positive cocci. The case was an elderly patient with joint surgery and ischaemic heart disease history. Infection resolved after adequate antibiotic therapy.

Infective anoproctitis in men having sex with men: Don't forget Mycoplasma genitalium.

OBJECTIVES: The aim was to describe the clinical characteristics of symptomatic anoproctitis and the occurrence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG) infections in a prospective cohort of MSM patients. METHODS: From February 2018 to January 2020, all consecutive patients presenting at the Leopold Bellan Proctology Institute of Saint-Joseph Hospital, Paris, France with symptoms of anoproctitis were tested on rectal samples for C. trachomatis (CT), N. gonorrhoeae (NG), M. genitalium (MG). Clinical, microbiological, biological data, STI risk factors, medical history and treatments were collected. RESULTS: Three hundred and sixty-five patients were included for suspected infective anoproctitis. CT was detected in 84/365 (23%) patients, NG in 45/365 (12%) and MG in 46/315 patients (15%), associated with macrolide resistance in 28/46 MG strains (61%). The most frequent symptoms were rectal pains, rectal bleeding, purulent discharge in 253 (79%), 191 (60%), and 164 (51%) of cases respectively. In comparison with MG infections, ulcerations, erythematous proctitis, rectorragia and false needs were more frequently described in CT infections, while purulent proctitis, functional pain and purulent discharge were more often observed in NG and CT anoproctitis. CONCLUSION: We found a high prevalence rate of STIs due to CT, NG, while MG detection was associated with a high rate of macrolide resistance in a cohort of MSM patients. Our results confirm that in cases of symptomatic anoproctitis, MG should be tested in association with other STI pathogens.

Evaluation of the Andromas matrix-assisted laser desorption ionization-time of flight mass spectrometry system for identification of aerobically growing Gram-positive bacilli.

Matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a rapid and simple microbial identification method. Previous reports using the Biotyper system suggested that this technique requires a preliminary extraction step to identify Gram-positive rods (GPRs), a technical issue that may limit the routine use of this technique to identify pathogenic GPRs in the clinical setting. We tested the accuracy of the MALDI-TOF MS Andromas strategy to identify a set of 659 GPR isolates representing 16 bacterial genera and 72 species by the direct colony method. This bacterial collection included 40 C. diphtheriae, 13 C. pseudotuberculosis, 19 C. ulcerans, and 270 other Corynebacterium isolates, 32 L. monocytogenes and 24 other Listeria isolates, 46 Nocardia, 75 Actinomyces, 18 Actinobaculum, 11 Propionibacterium acnes, 18 Propionibacterium avidum, 30 Lactobacillus, 21 Bacillus, 2 Rhodococcus equi, 2 Erysipelothrix rhusiopathiae, and 38 other GPR isolates, all identified by reference techniques. Totals of 98.5% and 1.2% of non-Listeria GPR isolates were identified to the species or genus level, respectively. Except for L. grayi isolates that were identified to the species level, all other Listeria isolates were identified to the genus level because of highly similar spectra. These data demonstrate that rapid identification of pathogenic GPRs can be obtained without an extraction step by MALDI-TOF mass spectrometry.

One-day prevalence of asymptomatic carriage of toxigenic and non-toxigenic Clostridioides difficile in 10 French hospitals.

BACKGROUND: Asymptomatic faecal carriage of Clostridioides difficile has been widely evaluated, but its prevalence across a wide range of clinical departments and related risk factors are not well described. The objectives of the PORTADIFF study were to evaluate the prevalence and identifying risk factors leading to asymptomatic carriage of both toxigenic and non-toxigenic C. difficile. METHODS: The PORTADIFF study was a 1-day prevalence study carried out in 10 different French hospitals. Adult patients, who agreed to participate, were included in this study and provided a fresh stool sample. C. difficile strains isolated from carriage were characterized by polymerase chain reaction (PCR) detection of tcdA, tcdB, cdtA and cdtB, and PCR ribotyping. RESULTS: In total, 721 patients were included in this study. The median age was 73 years (range 18-101 years) and the male/female ratio was 1.06. C. difficile (either toxigenic or non-toxigenic strains) was isolated from 79 (11%) patients; 42 (5.8%) strains were toxigenic. The prevalence rates of asymptomatic carriage ranged from 5% on surgical wards to 19% on long-term care wards. The main risk factors associated with asymptomatic carriage were antibiotic treatment within the preceding 3 months (81.8% vs 53.7%; P<0.01), hospitalization within the preceding 2 months (55.8% vs 33%; P<0.01), cumulative duration of hospital stay before study inclusion (mean 50.1 vs 34.5 days; P<0.047), and hospitalization on a ward with high global incidence of C. difficile infection. CONCLUSION: Eleven percent of hospitalized patients were asymptomatic carriers of toxigenic or non-toxigenic C. difficile, and may constitute a potential reservoir of C. difficile strains.

Evolution of anti-SARS-CoV-2 immune response in a cohort of French healthcare workers followed for 7 months.

OBJECTIVES: We aimed to understand the immune response among healthcare workers (HCWs) following SARS-CoV-2 infection, and to determine the infection prevalence during the first wave of the pandemic among workers in our hospital. METHODS: Determination of the serological status against SARS-CoV-2 (nucleocapsid) was offered to all HCWs. All HCWs with positive SARS-CoV-2 serology were proposed to be included in a longitudinal medical and serological follow-up (anti-spike) for 7months. RESULTS: We included 3062 HCWs; 256 (8.4%) were positive for anti-SARS-CoV-2 nucleocapsid IgG. Among them, early decrease in the anti-nucleocapsid antibody index was observed between the first (S1) and second (S2) serology samplings in 208 HCWs (84.2%). The initial anti-nucleocapsid IgG index seemed to be related to the HCWs' age. Seventy-four HCWs were included in the 7-month cohort study. Among them, 69 (90.5%) had detectable anti-spike IgG after 7months and 24 (32.4%) reported persistent symptoms consistent with post-acute COVID-19 syndrome diagnosis. CONCLUSION: The prevalence of serological positivity among HCWs was 6.7%. Infection should be followed by vaccination because of antibody decrease.

Epidemiology and clinical characteristics of Klebsiella spp. meningitis in France.

OBJECTIVES: To describe the epidemiology of Klebsiella spp. meningitis in France with respect to clinical and bacteriological data. METHODS: We performed a four-year multicenter, retrospective, observational study. The primary objective was to provide a clinical description of patients with Klebsiella spp. meningitis. Secondary objectives were to compare community-acquired meningitis and healthcare-associated meningitis and to analyze factors associated with mortality. RESULTS: We enrolled 131 patients with Klebsiella spp. meningitis. Eighty-two (62.6%) infections were reported following neurosurgery. Twenty-eight strains (21.4%) were resistant to third-generation cephalosporins (3GC). The median [IQR] cellularity was 980/mm3 [116-5550], the median protein level was 5.67 [1.62-9] g/L and the median CSF glucose level was 2.5 [0-3.4] mmol/L. The in-hospital mortality rate was 23.6%. Community-acquired meningitis isolates were more frequently susceptible to 3GC than isolates from healthcare-associated meningitis (89.2% versus 72%; P=0.04). Comorbidities reported for patients with community-acquired meningitis were mainly diabetes mellitus and liver cirrhosis. In multivariate analysis, focal neurological disorder at the time of diagnosis was the only factor associated with in-hospital mortality (P=0.01). CONCLUSIONS: Purulent meningitis caused by Klebsiella spp. needs to be considered in patients with community-acquired meningitis and preexisting conditions, as well as in case of meningitis following neurosurgical procedures.

Revisited distribution of nonfermenting Gram-negative bacilli clinical isolates.

Nonfermenting Gram-negative bacilli (NF-GNB) are ubiquitous environmental opportunistic bacteria frequently misidentified by conventional phenotypic methods. The aim of this study was to determine the distribution of NF-GNB species by 16 S rRNA gene sequencing (used as reference method) and to compare performances of biochemical tests and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). From nine French hospitals, 188 NF-GNB isolates (except P. aeruginosa and A. baumannii) were prospectively collected from 187 clinical samples between December 2008 and May 2009. By using the genotypic approach, 173 (92%) and 188 (100%) isolates were identified to the species and genus level, respectively. They covered 35 species and 20 genera, with a predominance of Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Pseudomonas putida group bacteria. Of the 173 species-level identified strains, concordant identification to the species-level was obtained for 75.1%, 83% and 88.9% of isolates with API 20 NE strip, the VITEK-2 (ID-GN card) system and MALDI-TOF-MS, respectively. By excluding S. maltophilia isolates accurately identified by the three methods, genus-level identification was much higher for MALDI-TOF-MS (92.9%), compared with API 20 NE and VITEK-2 (76.2% and 80.8%, respectively). In conclusion, MALDI-TOF-MS represents a rapid, inexpensive, and accurate tool for routine identification of NF-GNB in human clinical samples.

Favorable outcome after life-threatening meningococcal disease complicating influenza A(H1N1) infection.

PURPOSE: Neurological complications of influenza A(H1N1) have been reported in several patients since the onset of the pandemic in 2009. However, meningococcal disease complicating influenza A(H1N1) has not been reported. PATIENTS: Two patients were admitted to an intensive care unit (ICU) for altered mental status, fever, and rapidly spreading petechial purpura. They were diagnosed with meningococcal meningitis and/or meningococcemia and influenza A(H1N1) co-infection. CONCLUSIONS: Meningococcal disease presenting as meningitis and/or meningococcemia is among the potential complications of influenza A(H1N1) infection. Physicians should be aware of this co-infection, as it must be detected and treated promptly with antibiotics in addition to supportive care.

Is the second dose of vaccination useful in previously SARS-CoV-2-infected healthcare workers?

Vaccines are the most important public health measure to protect people from COVID-19 worldwide. In addition, healthcare workers account for a large number of infected people. Protecting this population from COVID-19 seems crucial to preserve healthcare systems. In a context of few doses available, serological assays could be useful to decide whether one or two doses are needed. Our results show that a first dose of BNT162b2 mRNA vaccine seems to act as a boost after SARS-CoV-2 infection in healthcare workers with a previous SARS-CoV-2 infection; a second dose might therefore not be required.

Relative faecal abundance of extended-spectrum ß-lactamase-producing Enterobacterales and its impact on infections among intensive care unit patients: a pilot study.

This pilot prospective study assessed the association between the faecal relative abundance of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) and the occurrence of ESBL-PE related infections. Twenty-four patients were included. The median ESBL relative abundance was 32.4%. The mean ESBL-PE relative abundance (ESBL-PE-RA) was more than five-fold higher in patients exposed during the last three months to antibiotics (P = 0.002). Furthermore, the mean ESBL relative abundance was more than two-fold higher in patients colonized with non-E. coli strains (P = 0.044). The mean ESBL-PE-RA was more than 10-fold higher for the concordant patients than for the discordant patients (59.1% vs 4.9%; P < 0.001).

Antimicrobial resistance of Listeria monocytogenes strains isolated from humans in France.

Susceptibility to antibiotics of 4,816 clinical L. monocytogenes strains isolated since 1926 was studied, and the temporal evolution of susceptibility to antibiotics was analyzed through several decades. The mechanisms of resistance in each resistant strain were studied. The prevalence of resistant strains was estimated at 1.27% among isolates from humans. Resistance to tetracyclines+ and fluoroquinolones was more common and has recently emerged. Although acquired resistance in clinical L. monocytogenes did not implicate clinically relevant antibiotics, the possibility of resistance gene transfers, the description of the first clinical isolate with high-level resistance to trimethoprim, and the recent increase in penicillin MICs up to 2 microg/ml reinforce the need for microbiological surveillance.

Expression of CTX-M-15 limits the efficacy of ceftolozane/tazobactam against Escherichia coli in a high-inoculum murine peritonitis model.

OBJECTIVES: Among carbapenem-sparing therapies, ceftolozane/tazobactam has been proposed for the treatment of infections due to CTX-M-15-producing Escherichia coli. However, few data exist on its in vivo activity in infections associated with a high bacterial inoculum. METHODS: We analysed ceftolozane/tazobactam activity against susceptible E. coli CFT073-RR and its CTX-M-15-producing transconjugant E. coli CFT073-RR Tc blaCTX-M-15, in vitro at low and high inocula, and in a high-inoculum murine model of peritonitis. RESULTS: Against E. coli CFT073-RR Tc blaCTX-M-15, ceftolozane/tazobactam bactericidal effect was impaired in vitro with only a minor inoculum effect; this translated into reduced activity compared with imipenem in the mouse peritonitis model. CONCLUSIONS: Combination of extended spectrum ß-lactamase expression and high inoculum size may be a clinical situation at risk of reduced bactericidal activity of ceftolozane/tazobactam.