Comparison of the in vitro activities of delafloxacin and comparators against Staphylococcus epidermidis clinical strains involved in osteoarticular infections: a CRIOGO multicentre retrospective study.

OBJECTIVES: Staphylococcus epidermidis bone and joint infections (BJIs) on material are often difficult to treat. The activity of delafloxacin has not yet been studied on S. epidermidis in this context. The aim of this study was to assess its in vitro activity compared with other fluoroquinolones, against a large collection of S. epidermidis clinical strains. METHODS: We selected 538 S. epidermidis strains isolated between January 2015 and February 2023 from six French teaching hospitals. One hundred and fifty-two strains were ofloxacin susceptible and 386 were ofloxacin resistant. Identifications were performed by MS and MICs were determined using gradient concentration strips for ofloxacin, levofloxacin, moxifloxacin and delafloxacin. RESULTS: Ofloxacin-susceptible strains were susceptible to all fluoroquinolones. Resistant strains had higher MICs of all fluoroquinolones. Strains resistant to ofloxacin (89.1%) still showed susceptibility to delafloxacin when using the Staphylococcus aureus 2021 CA-SFM/EUCAST threshold of 0.25 mg/L. In contrast, only 3.9% of the ofloxacin-resistant strains remained susceptible to delafloxacin with the 0.016 mg/L S. aureus breakpoint according to CA-SFM/EUCAST guidelines in 2022. The MIC50 was 0.094 mg/L and the MIC90 was 0.38 mg/L. CONCLUSIONS: We showed low delafloxacin MICs for ofloxacin-susceptible S. epidermidis strains and a double population for ofloxacin-resistant strains. Despite the absence of breakpoints for S. epidermidis, delafloxacin may be an option for the treatment of complex BJI, including strains with MICs of ≤0.094 mg/L, leading to 64% susceptibility. This study underlines the importance for determining specific S. epidermidis delafloxacin breakpoints for the management of BJI on material.

Cutibacterium namnetense osteosynthetic cervical spine infections: experience with two cases.

We report two uncommon cases of osteosynthetic cervical spine infection. Clinical patient features, microbiological strain characteristics, diagnostic methods, and treatment were analyzed. Both patients were male, and one had risk factors for surgical site infection. During surgery, perioperative samples were positive yielding an anaerobic microorganism identified as Cutibacterium namnetense by MALDI-TOF MS and confirmed by 16S rRNA/gyrB genes sequencing. All isolates were fully susceptible. C. namnetense osteosynthetic cervical spine infections are rare. Both cases were early surgical site infections. Bruker MALDI-TOF MS appears to be an excellent tool for rapid and accurate identification. Amoxicillin seems to be an option for the treatment.

Development and evaluation of automated synovial fluid total cell count on an Iris iQ® 200 for identifying patients at risk of septic arthritis.

Septic arthritis is a diagnostic emergency. The white blood cell (WBC) count, in synovial fluid (SF), can guide the diagnosis. From November 2021 to November 2022, we included 350 SF. The WBC count was performed with the Iris iQ® 200 compared with the manual method. Automated and manual counts displayed good correlation. However, a Bland Altman plot demonstrates a higher percentage difference at higher WBC counts. The use of Iris iQ® 200 for SF analysis enables a rapid and accurate assessment for WBC count. Its implementation would advantageously replace the long and tedious optical analysis in daily routine.

Misidentification of Cutibacterium namnetense as Cutibacterium acnes among clinical isolates by MALDI-TOF VitekMS: usefulness of gyrB sequencing and new player in bone infections.

The taxonomy modification of Propionibacterium sp. with the description of new species, especially Cutibacterium namnetense, raises the question of species distribution in routine clinical samples. We performed a retrospective study during 3 years before the implementation of MALDI-TOF. Two hundred sixty-nine isolates were included in the study. MALDI-TOF identification, 16S rRNA, and new developed gyrB partial sequencings were performed. The most representative species was C. acnes in 88% of the cases, regardless of the origin of the clinical sample. Eventually, we identified three C. namnetense strains, representing a 1.1% prevalence over the period of time, including two bone infections. MALDI-TOF databases should be regularly updated to incorporate new species. gyrB sequencing constitutes a both easy and relevant method to identify Cutibacterium sp. especially C. namnetense, a new player in bone infections.

Propionibacterium/Cutibacterium species-related positive samples, identification, clinical and resistance features: a 10-year survey in a French hospital.

A 10-year retrospective study of Propionibacterium/Cutibacterium-positive samples gathered from hospitalized patients was conducted at Nantes University hospital. A total of 2728 Propionibacterium/Cutibacterium-positive samples analyzed between 2007 and 2016 were included. Due to the implementation of MALDI-TOF identification in 2013, most non-Cutibacterium acnes isolates were identified a second time using this technology. Over that period, Cutibacterium acnes remained the most predominant species accounting for 91.5% (2497/2728) of the isolates, followed by Cutibacterium avidum (4.2%, 115/2728) and Cutibacterium granulosum (2.4%, 64/2728). Regarding the origin of samples, the orthopaedic department was the main Cutibacterium sample provider representing 51.9% (1415/2728) of all samples followed by the dermatology department (11.5%, 315/2728). Samples were recovered from various tissue locations: 31.5% (858/2728) from surgery-related samples such as shoulder, spine or hip replacement devices and 19.1% (520/2728) from skin samples. MALDI-TOF method revealed misidentification before 2013. Cutibacterium avidum was falsely identified as C. granulosum (n = 33). Consequently, MALDI-TOF technology using up-to-date databases should be preferred to biochemical identification in order to avoid biased species identification. Regarding antibiotic resistance, 14.7% (20/136) of C. acnes was resistant to erythromycin. 4.1% (41/1005) of C. acnes strains, 17.9% (12/67) of C. avidum strains and 3.6% (1/28) of C. granulosum strains were found resistant to clindamycin.

Acne fulminans and Cutibacterium acnes phylotypes.

BACKGROUND: Acne fulminans (AF) is a rare and severe form of inflammatory acne. It is characterized by a sudden worsening of acne with appearance of ulceronecrotic lesions, which can be associated with systemic signs. Its pathophysiology and the best therapeutic strategy are only partially known. OBJECTIVE: Our main objectives were to describe the clinical and biological profile of AF patients and to determine whether there was a difference in Cutibacterium acnes phylotype in AF compared to acne vulgaris. The secondary objective was to assess the efficacy of different therapies. METHODS: A retrospective observational study was conducted in all patients followed for AF in our department between 2008 and 2018. Bacteriological samples were taken from each patient to analyse C. acnes phylotype distribution. The therapeutic response was assessed using the ECLA and GEA scales. RESULTS: Fifteen patients with a median age of 15 years were included (12 men, 80%). A family history of acne was found in 86.7% of patients. Nine patients (60%) had isotretinoin-induced AF. Only one patient (6.7%) showed systemic signs. The bacteriological culture was positive for C. acnes in 80% of patients. The predominant phylotype was IA1 in 60% of patients, corresponding to the predominant phylotype in acne vulgaris. Only 33.3% of patients were in remission after a first-line treatment with systemic corticosteroids, alone or in combination. Seven patients were treated with biotherapy, including five successfully with secukinumab. CONCLUSION: Our results suggest that there is no specific C. acnes phylotype associated with AF, raising the hypothesis that acute inflammation associated with AF may be more related to an abnormal cutaneous innate immunity activation. The use of preventive strategies, the impact of combined treatments and an assessment of the role of biotherapies, especially anti-IL-17, in AF treatment remain to be more investigated.

Low prevalence of Cutibacterium acnes in prostatic tissue biopsies in a French hospital.

We evaluated the Cutibacterium acnes prevalence in prostatic biopsies and characterized the strains at a molecular level. 18 out of 36 biopsies (50%) were sterile after seven days in culture. C. acnes was observed in only two biopsies. Its prevalence was low (5.6%). Finally, the molecular characterization revealed diverse clusters including phylotypes IA1, IB and II.

Cutibacterium acnes phylotypes diversity loss: a trigger for skin inflammatory process.

BACKGROUND: Acne has long been understood as a multifactorial chronic inflammatory disease of the pilosebaceous follicle, where Cutibacterium acnes (subdivided into six main phylotypes) is a crucial factor. In parallel, the loss of microbial diversity among the skin commensal communities has recently been shown as often accompanied by inflammatory skin disorders. OBJECTIVE: This study investigated the association of C. acnes phylotype diversity loss and the impact on Innate Immune System (IIS) activation. METHODS: The IIS response of skin after incubation with phylotypes IA1, II or III individually and with the combination of IA1 + II + III phylotypes, was studied in an in vitro skin explant system. The inflammatory response was monitored by immunohistochemistry and ELISA assays, targeting a selection of Innate Immune Markers (IIMs) (IL-6, IL-8, IL-10, IL-17, TGF-ß). RESULTS: IIMs were significantly upregulated in skin when being incubated with phylotype IA1 alone compared with the combination IA1 + II + III. In parallel, ELISA assays confirmed these results in supernatants for IL-17, IL-8 and IL-10. CONCLUSION: We identify the loss of C. acnes phylotype diversity as a trigger for IIS activation, leading to cutaneous inflammation. These innovative data underline the possibility to set up new approaches to treat acne. Indeed, maintaining the balance between the different phylotypes of C. acnes may be an interesting target for the development of drugs.

Taxonomy and phylogeny of Cutibacterium (formerly Propionibacterium) acnes in inflammatory skin diseases.

Since its discovery, Propionibacterium acnes has undergone various name changes, and has been known since 2016, as Cutibacterium acnes. Herein we set out the history and rational of these taxonomic changes together with a description of a new genus, Cutibacterium, which includes five species within the cutaneous ecosystem. Modern microbiological techniques allow finer distinction between species and subspecies while also enabling the identification of separate subtypes within the population of Cutibacterium acnes. Phylogeny and molecular typing techniques thus provide a better understanding of the subtypes involved in certain inflammatory skin diseases, including acne, folliculitis and progressive macular hypomelanosis.

Tetracycline use in the community may promote decreased susceptibility to quinolones in Escherichia coli isolates.

We previously found that the hospital use of tetracyclines is associated with quinolone resistance in hospital isolates of Enterobacteriaceae. Tetracyclines are heavily used in the community. Our aim was to assess whether their use in the community favors quinolone resistance in community isolates of Escherichia coli. Monthly data of community antibiotics use and E. coli quinolone resistance in a 1.3 million inhabitant French area were obtained from 2009 to 2014, and were analyzed with autoregressive integrated moving average (ARIMA) models. Quinolone use decreased from 10.1% of the total antibiotic use in 2009 to 9.3% in 2014 (trend, - 0.016; p-value < 0.0001), while tetracycline use increased from 16.5% in 2009 to 17.1% in 2014 (trend, 0.016; p < 0.0001). The mean (95% confidence interval) monthly proportions of isolates that were non-susceptible to nalidixic acid and ciprofloxacin were 14.8% (14.2%-15.5%) and 9.5% (8.8%-10.1%), respectively, with no significant temporal trend. After adjusting on quinolone use, tetracycline use in the preceding month was significantly associated with nalidixic acid non-susceptibility (estimate [SD], 0.01 [0.007]; p-value, 0.04), but not with ciprofloxacin non-susceptibility (estimate [SD], 0.01 [0.009]; p-value, 0.23). Tetracycline use in the community may promote quinolone non-susceptibility in E. coli. Decreasing both tetracycline and quinolone use may be necessary to fight against the worldwide growth of quinolone resistance.

Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates.

While the commensal bacterium Propionibacterium acnes (P. acnes) is involved in the maintenance of a healthy skin, it can also act as an opportunistic pathogen in acne vulgaris. The latest findings on P. acnes shed light on the critical role of a tight equilibrium between members of its phylotypes and within the skin microbiota in the development of this skin disease. Indeed, contrary to what was previously thought, proliferation of P. acnes is not the trigger of acne as patients with acne do not harbour more P. acnes in follicles than normal individuals. Instead, the loss of the skin microbial diversity together with the activation of the innate immunity might lead to this chronic inflammatory condition. This review provides results of the most recent biochemical and genomic investigations that led to the new taxonomic classification of P. acnes renamed Cutibacterium acnes (C. acnes), and to the better characterisation of its phylogenetic cluster groups. Moreover, the latest data on the role of C. acnes and its different phylotypes in acne are presented, providing an overview of the factors that could participate in the virulence and in the antimicrobial resistance of acne-associated strains. Overall, this emerging key information offers new perspectives in the treatment of acne, with future innovative strategies focusing on C. acnes biofilms and/or on its acne-associated phylotypes.

Association between dementia and reduced walking ability and 30-day mortality in patients with extended-spectrum beta-lactamase-producing Escherichia coli bacteremia.

Previous studies have shown controversial results of factors associated with short-term mortality in patients with extended-spectrum beta-lactamase (ESBL)-producing E. coli bacteremia and no research has investigated the impact of the geriatric assessment criteria on short-term mortality. Our objective was to determine whether dementia and walking ability are associated with 30-day mortality in patients with ESBL-producing E. coli bacteremia. All blood bottle cultures, analyzed from January 2008 to April 2015, in the Bacteriology Department of a 2,600-bed, university-affiliated center, Nantes, France, were retrospectively extracted. Factors associated with short-term mortality in patients with ESBL-producing E. coli bacteremia: 140 patients with an ESBL-producing E. coli bloodstream infection were included; 22 (15.7%) patients died within 30 days following the first positive blood bottle culture of ESBL-producing E.coli. In multivariate analysis, a reduced ability to walk (OR = 0.30; p = 0.021), presence of dementia (OR = 54.51; p = 0.040), a high Sepsis-related Organ Failure Assessment (SOFA) score (OR = 1.69; p < 0.001), presence of neutropenia (OR = 12.94; p = 0.049), and presence of a urinary tract infection (OR = 0.07; p = 0.036), were associated with 30-day mortality. Our findings provide new data showing an independent association between 30-day mortality with dementia and reduced walking ability, in patients with ESBL-producing E. coli bacteremia. These criteria should be considered in the therapeutic management of patients with ESBL-producing E. coli bacteremia.

Characterization of Staphylococcus caprae Clinical Isolates Involved in Human Bone and Joint Infections, Compared with Goat Mastitis Isolates.

Staphylococcus caprae is an emerging microorganism in human bone and joint infections (BJI). The aim of this study is to describe the features of S. caprae isolates involved in BJI (H for human) compared with those of isolates recovered in goat mastitis (A for animal). Fourteen isolates of each origin were included. Identifications were performed using a Vitek 2 GP ID card, tuf gene sequencing, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) Vitek MS. Molecular typing was carried out using pulsed-field gel electrophoresis (PFGE) and DiversiLab technology. The crystal violet method was used to determine biofilm-forming ability. Virulence factors were searched by PCR. Vitek MS technology provides an accurate identification for the two types of isolates compared to that of gold-standard sequencing (sensitivity, 96.4%), whereas the Vitek 2 GP ID card was more effective for H isolates. Molecular typing methods revealed two distinct lineages corresponding to the origin despite few overlaps: H and A. In our experimental conditions, no significant difference was observed in biofilm production ability between H and A isolates. Nine isolates (5 H isolates and 4 A isolates) behaved as weak producers while one A isolate was a strong producer. Concerning virulence factors, the autolysin atlC and the serine aspartate adhesin (sdrZ) genes were detected in 24 isolates (86%), whereas the lipase gene was always detected, except in one H isolate (96%). The ica operon was present in 23 isolates (82%). Fibrinogen-binding (fbe) or collagen-binding (cna) genes were not detected by using primers designed for Staphylococcus aureus or Staphylococcus epidermidis, even in low stringency conditions. Although S. caprae probably remains underestimated in human infections, further studies are needed to better understand the evolution and the adaptation of this species to its host.

Gram-negative prosthetic joint infections managed according to a multidisciplinary standardized approach: risk factors for failure and outcome with and without fluoroquinolones.

OBJECTIVES: To describe the outcome and risk factors for treatment failure of 76 Gram-negative bacilli (GNB) prosthetic joint infections (PJIs) managed with a curative intent according to a standardized protocol derived from published guidelines. METHODS: We analysed data from all the cases of GNB-PJI treated surgically over an 8 year period. Treatment failure was defined as persistence or recurrence of PJI signs during follow-up, resulting in additional surgery and/or antibiotic administration or death. RESULTS: Treatment failure within the follow-up period (median = 2.6 years) was observed in 16 of 76 (21.1%) patients. The failure rate was similar whether the patients were treated with fluoroquinolones in the whole cohort (22.4% versus 16.7%, P = 0.75) and after stratification according to the surgical procedure. The low failure rate observed in patients not receiving fluoroquinolones might be explained by the standardized attitude of maintaining intravenous ß-lactams throughout treatment duration (median = 90 days). In multivariate analysis, C-reactive protein level ≥175 mg/L was significantly associated with treatment failure (adjusted HR = 7.75, 95% CI = 2.66-22.59, P < 0.0001). CONCLUSIONS: Management according to standardized procedures may improve the prognosis of GNB-PJI. Intravenous ß-lactams, continued for 3 months, should be considered an effective alternative to fluoroquinolones.

Innate immune evasion of Escherichia coli clinical strains from orthopedic implant infections.

Escherichia coli is one of the first causes of Gram-negative orthopedic implant infections (OII). Those infections, usually hematogenous, mostly originate from the urinary tract. We investigated the strategies developed by E. coli in this context to evade host innate immune responses, i.e. complement and polymorphonuclear neutrophils (PMN). Twenty strains from OII were compared with 20 strains from bacteremia in patients with non-infected orthopedic implant. In both groups, 6/20 (30 %) strains lysed PMNs, due to the production of the pore-forming toxin α-hemolysin (HlyA). For the others, resistance to phagocytic killing by PMN was not significantly different between both groups. In contrast, resistance to complement-mediated serum killing was significantly higher in OII strains than in the others (65 % vs 10 %; P <0.001). In E. coli, different mechanisms have been involved in complement resistance. Here, serum resistance was not linked to a group 2 capsule, or a loss of outer membrane permeability, or the recruitment of the complement inhibitor C4bp, but was significantly associated with the synthesis of long-chain LPS, regardless of the O-antigen. Thus, serum resistance could promote seeding of peri-implant tissues by helping E. coli to either persist in blood and reach the site of infection or overcome localized complement activation.

Systematic analysis of the relationship between antibiotic use and extended-spectrum beta-lactamase resistance in Enterobacteriaceae in a French hospital: a time series analysis.

The influence of hospital use of antibiotics other than cephalosporins and fluoroquinolones on extended-spectrum beta-lactamase (ESBL) resistance among Enterobacteriaceae is poorly known. Our objective was to explore the association between ESBL and hospital use of various classes of antibacterial agents. The relationship between monthly use of 19 classes of antibacterial agents and incidence of nosocomial ESBL-producing Enterobacteriaceae in a French hospital was studied between 2007 and 2013. Five antibiotic classes were significantly and independently associated with ESBL resistance. Uses of tetracyclines (link estimate ± SE, 0.0066 ± 0.0033), lincosamides (0.0093 ± 0.0029), and other antibacterial agents (0.0050 ± 0.0023) were associated with an increased incidence, while nitrofurantoin (-0.0188 ± 0.0062) and ticarcillin and piperacillin with or without enzyme inhibitor (-0.0078 ± 0.0031) were associated with a decreased incidence. In a multivariate model including 3rd- and 4th-generation cephalosporins, fluoroquinolones, amoxicillin, and amoxicillin-clavulanate, 3rd- and 4th-generation cephalosporins (0.0019 ± 0.0009) and fluoroquinolones (0.0020 ± 0.0008) were associated with an increased ESBL resistance, whereas amoxicillin and amoxicillin-clavulanate were not. Hospital use of tetracyclines and lincosamides may promote ESBL resistance in Enterobacteriaceae. Nitrofurantoin and ticarcillin and piperacillin with or without enzyme inhibitor should be considered as potential alternatives to broad-spectrum cephalosporins and fluoroquinolones to control the diffusion of ESBL resistance.

Escherichia coli antibiotic resistance in emergency departments. Do local resistance rates matter?

Ciprofloxacin and cotrimoxazole are recommended to treat uncomplicated pyelonephritis and uncomplicated cystitis, respectively, provided that local resistance rates of uropathogens do not exceed specified thresholds (10 and 20 %, respectively). However, Escherichia coli resistance rates in Emergency Departments (ED) remain poorly described. Our objectives were to assess E. coli ciprofloxacin and cotrimoxazole resistance rates in EDs of a French administrative region, and to determine if resistance rates differ between EDs. This was a retrospective study of E. coli urine isolates sampled in ten EDs between 2007 and 2012. The following risk factors for resistance were tested using logistic regression: ED, sex, age, sampling year, sampling month. A total of 17,527 isolates were included. Ciprofloxacin local resistance rates (range, 5.3 % [95 % CI, 4.0-7.1 %] to 11.7 % [95 % CI, 5.2-23.2 %]) were ≤10 % in nine EDs in 2012. Five EDs were risk factors for ciprofloxacin resistance, as were male sex, age and sampling in April or October. Cotrimoxazole local resistance rates (range, 13.3 % [95 % CI, 6.3-25.1 %] to 20.4 % [95 % CI, 18.9-22.0 %]) were ≤20 % in seven EDs in 2012. Five EDs were risk factors for cotrimoxazole resistance, as were age, sampling between October and December, and sampling in 2011 and 2012. We found a significant variability of E. coli ciprofloxacin and cotrimoxazole resistance rates among EDs of a small region. These differences impact on the feasibility of empirical treatment of urinary tract infections with ciprofloxacin or cotrimoxazole in a given ED. Continuous local survey of antibacterial resistance in ED urinary isolates is warranted to guide antibacterial therapy of urinary tract infections.