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.

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.

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.

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.

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.

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.

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.

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).

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.

Clinical evaluation of subcutaneous administration of cefepime.

OBJECTIVES: Cefepime is a fourth-generation cephalosporin active against Pseudomonas aeruginosa and most Enterobacteriaceae. Intravenous (IV) administration is the standard route of prescription. However, subcutaneous administration (SC) may represent an interesting alternative. We aimed to evaluate SC administration of cefepime versus the IV route in geriatric patients. PATIENTS AND METHODS: Multicenter retrospective analysis in patients treated with cefepime by SC route who underwent plasma concentration monitoring. RESULTS: Twelve patients were included in the SC group and matched to 12 patients in the IV group. The median and mean Cmin levels were 29.05mg/L [14.2-48.2]; 33.4mg/L (±21.8) in the SC group and 31.9mg/L [26.5-51.7]; 39.6mg/L (±27) (P=NS) in the IV group. No local SC administration-related complications were reported. No relapse was observed over six months of follow up. CONCLUSION: Subcutaneous use of cefepime seems to have the same clinical and microbiological effectiveness as parenteral administration.

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.

Infections caused by naturally AmpC-producing Enterobacteriaceae: Can we use third-generation cephalosporins? A narrative review.

The burden of antibiotic-resistant infections among Gram-negative bacteria is increasing. Resistance to third-generation cephalosporins (3GCs) in Enterobacteriaceae is mainly conferred by the acquisition of ß-lactamases or by deregulation of natural genetically-encoded ß-lactamase enzymes. Enterobacteriaceae such as Enterobacter spp., Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (ESCPM group) possess chromosomally-encoded inducible AmpC ß-lactamases. AmpC can be overproduced as a response to ß-lactam antibiotic exposure or by constitutive dysfunction of the AmpC regulation system. This overproduction can lead to the inactivation of 3GCs. Based on small clinical studies, international guidelines and expert recommendations suggest that 3GCs should be avoided as definitive therapy for infections caused by ESCPM group organisms. In this narrative review, we discuss the published literature and evaluate the risk related to 3GC use in the case of documented ESCPM infection.

Clinical impact of rapid bacterial identification by MALDI-TOF MS combined with the bêta-LACTA™ test on early antibiotic adaptation by an antimicrobial stewardship team in bloodstream infections.

BACKGROUND: Bloodstream infections (BSI) can potentially be life-threatening infections and are associated with a high crude mortality, moreover with an inappropriate first-line antibiotic therapy. Bacterial resistance is more and more frequently observed. New strategies of BSI management are urgently needed. MATERIALS AND METHODS: During an 18-months period, we prospectively evaluated the clinical impact of rapid bacterial identification by MALDI-TOF MS technology combined with an antimicrobial stewardship team (AST) intervention. Furthermore, during an 8-months period, we combined this strategy with the rapid detection of third-generation cephalosporin (3GC) resistance by the Bêta-LACTA™ test (BLT) directly on blood cultures. We then evaluated the theoretical impact of BLT on antibiotic therapy adaptation and establishment of infection control measures. RESULTS: A total of 335 blood cultures were enrolled during the study. MALDI-TOF MS gave accurate identification for 301 blood cultures (89,8%) and led to early antibiotic therapy adaptation for 73 episodes (21.8%). BLT was performed on 141 blood cultures, revealing 28 3GC-resistant bacteria (19.9%). Twenty-one patients (75%) received a non-adapted first-line treatment. The antibiotic therapy adaptation was delayed by 28.1 hours and the establishment of infection control measures by 35 hours with antimicrobial susceptibility testing, compared to the theoretical adaptation with BLT result. CONCLUSIONS: These tools can be included in a strategy of bloodstream infections management for a better patient care, optimizing and saving the use of antibiotics, notably carbapenems as well as diminishing the spread of multi-drug resistant bacteria by applying rapidly infection control measures.

Clinical diagnostic and therapeutic aspects of 221 consecutive anorectal Chlamydia trachomatis and Neisseria gonorrhoeae sexually transmitted infections among men who have sex with men.

OBJECTIVES: Proctitis caused by Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are known as sexually transmitted infections (STI). This study describes their clinical, diagnostic and therapeutic aspects. METHODS: Between 01/2013-03/2015, all MSM consulting for proctitis at proctology Institute-Saint-Joseph's Hospital, Paris, were included. Demographic, past-medical history, STI status and medical treatment were collected. Detection of CT/NG was performed by Transcription-Mediated Amplification (TMA) and antimicrobial susceptibilities for Ng by agar diffusion method. RESULTS: On 441 rectal samples collected, 221 (50.1%) were positive: 109 Ct (49.3%), 70 Ng (31.7%), 42 positive for both etiologies (19%). Among Ng infections, no resistance was detected to azithromycin and ceftriaxone. However, 84 strains (43.2%) were resistant to fluoroquinolones. More than one episode was diagnosed for 10 (5.1%) and 12 (6.2%) patients with CT and NG infections respectively. Anal abscesses were found for 27 (13.9%) patients, and 14 (7.2%) of them underwent surgery for anal fistula. CONCLUSIONS: The prevalence of CT/NG anorectal infections described is high on symptomatic patients, and a significant level of abscess was reported. These results confirm the interest of the association of recommended antibiotics excluding quinolones. Prospective studies would be relevant on complicated forms of anorectal infections.

Carriage of ESBL-producing Enterobacteriaceae in French hospitals: the PORTABLSE study.

BACKGROUND: Currently, contact precautions are recommended for patients colonized or infected with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Recent studies have challenged this strategy. This study aimed to assess the rate of ESBL-PE faecal carriage among hospitalized patients according to type of hospital ward, and to identify risk factors associated with carriage. METHODS: A point prevalence study was conducted in five different types of hospital ward [medical, surgical, intensive care unit (ICU), after care and rehabilitation, and geriatric] in eight French hospitals. All patients included in the study provided a fresh stool sample. RESULTS: In total, 554 patients were included in the study, with a median age of 73 years (range 60-82 years). The overall faecal carriage rate of ESBL-PE was 17.7%. The most frequently encountered species among ESBL-PE was Escherichia coli (71.4%), followed by Klebsiella pneumoniae (14.3%). Risk factors associated with ESBL-PE faecal carriage on univariate analysis were: living in the Paris region (P<0.01) and hospitalization on a geriatric ward (P<0.01). Interestingly, the cumulative duration of hospital stay before screening was not associated with a significantly higher prevalence of ESBL-PE carriage, regardless of ward type. The ESBL-PE colonization rate was much higher for patients hospitalized on geriatric wards (28.1%) and ICUs (21.7%) compared with those for patients hospitalized on surgical wards (14.8%), medical wards (12.8%) or aftercare and rehabilitation (11.2%). CONCLUSION: The overall prevalence of ESBL-PE faecal carriage was 17.7%, with only 21% of patients identified previously as carriers. The delay between admission and screening was not associated with an increase in ESBL-PE faecal carriage.

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.