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.

Clostridial prosthetic joint infections: A series of 16 cases and literature review.

OBJECTIVES: Prosthetic joint infections (PJIs) due to the Clostridium species have not been widely investigated. We aimed to characterize these uncommon infections. METHODS: We conducted a retrospective study between 2003 and 2020 in six French hospitals combined with a review of the literature. RESULTS: The main conclusions obtained from the 16 patients included were reinforced by the literature analysis: (i) Clostridium perfringens was the most frequently involved species, (ii) patients presented an advanced age at the time of prosthesis placement and infection, (iii) most of the infections were early- or delayed-onset, (iv) the prognosis for these PJIs remains poor, (v) when performed (n = 5), DAIR with 12-week antimicrobial therapy led to a favorable outcome in 80% of cases. CONCLUSIONS: Given the low incidence of this infection, our work represents the largest series of clostridial PJIs reported to date and highlights some specificities of these infections. Further prospective studies are needed to confirm these results.

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.

2022 SPILF - Clinical Practice guidelines for the diagnosis and treatment of disco-vertebral infection in adults.

These guidelines are an update of those made in 2007 at the request of the French Society of Infectious Diseases (SPILF, Société de Pathologie Infectieuse de Langue Française). They are intended for use by all healthcare professionals caring for patients with disco-vertebral infection (DVI) on spine, whether native or instrumented. They include evidence and opinion-based recommendations for the diagnosis and management of patients with DVI. ESR, PCT and scintigraphy, antibiotic therapy without microorganism identification (except for emergency situations), therapy longer than 6 weeks if the DVI is not complicated, contraindication for spinal osteosynthesis in a septic context, and prolonged dorsal decubitus are no longer to be done in DVI management. MRI study must include exploration of the entire spine with at least 2 orthogonal planes for the affected level(s). Several disco-vertebral samples must be performed if blood cultures are negative. Short, adapted treatment and directly oral antibiotherapy or early switch from intravenous to oral antibiotherapy are recommended. Consultation of a spine specialist should be requested to evaluate spinal stability. Early lifting of patients is recommended.

Assessment of the Performance of the Aptima Bacterial Vaginosis Assay Over a 3-Month Period in a French Hospital.

Bacterial vaginosis (BV) is the most common cause of abnormal vaginal discharge. BV represents a dysbiosis with the acquisition of a diverse community of anaerobic bacteria and a reduction in lactobacilli burden. Our objective was to evaluate the Aptima BV assay kit for the diagnosis of BV. From May to August 2019, we enrolled outpatients and inpatients, including nonpregnant women above 18 with vaginosis symptoms, consulting at Nantes University hospital. The Aptima BV assay measures the loads of Gardnerella vaginalis, Atopobium vaginae, and Lactobacillus species in relation to overall bacterial load. The Aptima BV assay was compared to Nugent scoring (NS). A total of 456 women were enrolled, and 347 patients met the inclusion criteria with data available for the analysis. NS was used to classify the samples and 144 (41.5%) samples were classified as normal (NS = 0-3), 45 (13%) as BV (NS = 7-10), 38 (11%) presented an intermediate vaginal microbiota (3 < NS < 7), 79 (22.7%) had various bacteria (excluding vaginal flora), 29 (8.3%) had insufficient bacterial density, and 12 (3.5%) had a predominance of yeasts. The Aptima BV kit displayed a sensitivity of 91.1% and specificity of 94.4% with a positive predictive value (PPV) of 83.7% and a negative predictive (NPV) value of 97.1%. The results of this monocentric retrospective study show that Aptima BV kit has a good diagnostic correlation compared to standard of care for dysbiotic diagnosis cases. IMPORTANCE The possibility exists of the involvement of a new molecular test in the routine algorithm of bacterial vaginosis diagnosis in microbiology laboratories. This manuscript reports on our experience, and we propose an organization combining Nugent scoring and molecular testing, especially for intermediate Nugent scores.

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.

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.

Catheter-related bloodstream infection due to Tsukamurella pulmonis identified by MALDI-TOF spectrometry, 16S rRNA gene sequencing, and secA1 gene sequencing in an immunocompromised child: a case report and literature review.

Tsukamurella species are Gram-positive bacilli related to aerobic Actinomyces. Originally reported from the environment, Tsukamurella species have also been described in human infections, especially in bacteremia. A literature review analysis revealed that Tsukamurella spp. are often initially considered as contaminant microorganisms, especially due to bacterial identification issues. Here, we report a catheter-related bloodstream infection in an immunocompromised child caused by Tsukamurella pulmonis. Matrix-Assisted Laser Desorption/Ionization-Time Of Flight (MALDI-TOF) mass spectrometry allowed rapid genus-level identification and contributed to better patient care. However, accurate species-level identification required 16S rRNA gene sequencing and secA1 gene sequencing. Considering the increased number of Tsukamurella infections, the implementation of new Tsukamurella species in MALDI-TOF databases is required to be more discriminant.

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.

Risk factors for Cutibacterium acnes spinal implant-associated infection: a case-case-control study.

OBJECTIVES: The aim was to determine the characteristics of patients who developed Cutibacterium acnes spinal implant-associated infection (SIAI) and the associated risk factors. METHODS: We conducted two parallel case-control studies comparing 59 patients with SIAI caused by C. acnes (cases 1) and 93 patients with SIAI caused by other microorganisms (cases 2) diagnosed during 2010-2015 with 302 controls who underwent spinal instrumentation without subsequent infection. RESULTS: Late-onset infections (median time to diagnosis, 843 days versus 23 days; p < 0.001) were more common in cases 1 than in cases 2. However, 20/59 (34%) of cases 1 occurred within the first 3 months after the index surgery. In addition, cases 1 were less likely to have fever (27%, 16/59 versus 58%, 54/93; p 0.001) or wound inflammation (39%, 23/59 versus 72%, 67/93; p < 0.001). Moreover, 24/59 (40%) of cases 1 presented with polymicrobial infections, and staphylococcal pathogens accounted for 22/24 (92%) of the co-infections. By comparing and contrasting the two multivariate risk models (cases 1 versus controls and cases 2 versus controls), the following factors associated with C. acnes SIAI development were identified: age <54 years (adjusted odds ratio (aOR) 2.43, 95% confidence interval (CI) 1.09-5.58, p 0.03), a body mass index <22 kg/m2 (aOR 2.47, 95% CI 1.17-5.29, p 0.02), and thoracic instrumentation (aOR 16.1, 95% CI 7.57-37.0, p < 0.001). CONCLUSIONS: Future therapeutic and prophylactic studies on C. acnes SIAI should focus on young, thin patients who undergo spinal instrumentation procedures involving the thoracic spine.

Prevalence of Haemophilus influenzae with alteration of PBP 3 sequence over a 1-year period in a French hospital: focus on a clinical failure after ceftriaxone treatment.

Among 547 Haemophilus influenzae isolates recovered in our center, 45 displayed a phenotype of loss of PBP 3 affinity (8.2%). Two isolates with 6 substitutions in PBP 3 showed decreased susceptibility to third-generation cephalosporins. Clinical data revealed clinical failure after ceftriaxone treatment in a context of bronchitis in a patient with pulmonary sarcoidosis.

Characteristics and outcome of multidrug-resistant tuberculosis in a low-incidence area.

OBJECTIVES: To characterize multidrug-resistant tuberculosis (MDR-TB) patients treated in a low endemic area in France and to determine risk factors for resistance. We also analyzed the efficacy and tolerability of tuberculosis (TB) treatment. METHODS: Between 2002-2013, all MDR-TB patients diagnosed in western France (hospitals belonging to the GERICCO group) were retrospectively included, with a follow-up period running until 2016. A case-control study (1:2), matched according to age, sex, and year of diagnosis, was performed to assess socio-demographic and clinical data, treatment strategies, and outcomes for the MDR-TB patients and controls treated for drug-susceptible tuberculosis during the same period. RESULTS: Of 134 TB patients, 44 were MDR-TB and 90 were drug-susceptible TB. Of the 44 MDR-TB patients (35 MDR and nine extensively drug-resistant [XDR]), 33 (75%) were males; the median age was 33 years; and 27 (61%) were born in Eastern Europe. Prior treatment failure was more frequently reported for XDR-TB (8/9) in Georgian patients. In multivariate analysis, risk contacts and prior TB history were associated with MDR-TB. Treatment failure was associated with MDR/XDR-TB and miliary TB. CONCLUSION: In western France, MDR-TB more frequently occurred in recent migrants from high-risk countries with a previous history of at-risk contact with other MDR-TB patients or previous TB treatment failure.

Bacteriological relevance of linezolid vs. vancomycin in postoperative empirical treatment of osteoarticular infections: a retrospective single-center study.

BACKGROUND: In 2015, our center replaced vancomycin with linezolid for the postoperative empirical treatment of osteoarticular infections (OAI). OBJECTIVES: To assess the bacteriological relevance of linezolid for orthopedic postoperative probabilistic antibiotic therapy. METHODS: Analysis of an observational cohort of patients empirically treated with a combination of linezolid and piperacillin/tazobactam during the immediate postoperative stage for an OAI between July 1st 2015 and July 1st 2016, in a French reference center. RESULTS: Seventy-seven of 126 patients who received a probabilistic postoperative combination of linezolid with piperacillin/tazobactam had microbiological proof of infection. Sixty-six of 77 OAI involved material, including an osteosynthesis in 45 cases (68%) and prosthesis in 21 cases (32%). Infection was due to Gram-positive bacteria in 62 cases (80.5%), mostly S. aureus (n=32, 41.6%), and S. epidermidis (n=14, 18.2%) accounting for 74.2% of Gram-positive bacteria. Among 14 OAI due to S. epidermidis, 11 (78.6%) were due to methicillin-resistant strains. All the S. aureus and S. epidermidis strains were susceptible to linezolid (MICs ≤ 4 mg/L), except in one patient previously treated with linezolid who was infected with a linezolid-resistant S. epidermidis strain (MIC > 256 mg/L). CONCLUSION: Linezolid can be used empirically in postoperative antibiotic therapy of OAI before obtaining definitive microbial results. Although linezolid resistance is rare in this population, previous oxazolidinone treatment should be documented before initiation of probabilistic postoperative treatment to highlight potential linezolid resistance.

Assessment of the automated multiplex-PCR Unyvero i60 ITI® cartridge system to diagnose prosthetic joint infection: a multicentre study.

OBJECTIVES: Prosthetic joint infections (PJI) are responsible for significant morbidity and mortality and their number continues to rise. Their management remains complex, especially the microbiological diagnosis. Besides 'homemade' tests developed by several teams, new molecular biology methods are now available with different analytical performance and usability. METHODS: We studied the performances of one of these tests: ITI® multiplex PCR (mPCR) by the Curetis® company and compared it to either 'optimized' culture or 16S rRNA PCR. We performed a retrospective multicentre study to assess the contributions of mPCR in the diagnosis of PJI. We randomly selected 484 intraoperative specimens among 1252 of various types (biopsy, bone, tissue around the prosthesis, synovial fluid) from 251 patients in seven different hospitals. Each sample was treated according to the recommendations of the manufacturer. RESULTS: In all, 154 out of 164 (93.9%) samples negative in culture were negative with the mPCR. Among the 276 positive samples in culture, 251 (90.9%) were monomicrobial, of which 119 (47.4%) were positive with the mPCR, and 25 (9.1%) were polymicrobial, of which 12 (48%) were positive with the mPCR. The concordance rate of mPCR with culture was 58.1% (53.6%-62.7%) and the concordance rate with 16S rRNA PCR was 70.1% (65.5%-74.6%). CONCLUSION: This new standardized molecular test showed a lack of detection when the bacterial inoculum was low (number of positive media per sample and number of colonies per media) but can be useful when patients have received antibiotic therapy previously.

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.