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.

[Epidemiology of healthcare-associated infections due to MRSA in Brest University Hospital from 2004 to 2007. Impact of hydroalcoholic gel and antibiotics consumptions]. / Épidémiologie des infections nosocomiales à SARM au CHU de Brest du 1(er) janvier 2004 au 31 décembre 2007. Impact des consommations de produits hydroalcooliques et d'antibiotiques.

UNLABELLED: The fight against healthcare-associated infections is based on preventive measures of multidrug resistant bacteria diffusion. Hand hygiene is the simplest and the most effective preventive measure to reduce cross-transmission of infectious agents. Hydroalcoholic solutions for hand hygiene was recently introduced in the University Hospital of Brest (France). The aims of the study were: to describe the epidemiology of healthcare-associated infections due to methicillin-resistant Staphylococcus aureus (MRSA); to determine the annual consumptions of antistaphylococcal antibiotics; and to discuss the relation between consumption of antiseptic products or antibiotics and the epidemiology of MRSA. METHODS: A retrospective epidemiological and pharmaco-epidemiological study was realized from January 2004 to December 2007 in the University Hospital of Brest (France). It allowed to bring to light the cases of healthcare-associated infections due to MRSA and to quantify the consumptions of hang hygiene products and antistaphylococcal antibiotics. RESULTS: this retrospective study showed a decrease of healthcare-associated infections due to MRSA and an increase of the consumption of hydroalcoholic solutions. Antistaphylococcal resistance rates also decreased in a context of fall of the global antibiotics consumption in the hospital.

Intrafamilial transmission of extended-spectrum-beta-lactamase-producing Escherichia coli and Salmonella enterica Babelsberg among the families of internationally adopted children.

OBJECTIVES: International adoption from developing countries has become an increasing phenomenon in recent years. Given the high prevalence of multidrug-resistant (MDR) bacteria in these countries, the adopted children represent a group at risk for both carriage and infection with MDR bacteria. The dynamics of intrafamilial transmission of MDR bacteria after adoption was studied in a prospective study from January 2002 to January 2005. METHODS: Stool samples, taken at the first visit to the outpatient adoption practice and subsequently every month, from the adopted children of an orphanage of Bamako (Mali) and from all the members of their adoptive families were screened for MDR bacteria and bacterial pathogens. Bacteria were characterized by standard biochemical methods, disc diffusion antibiograms, PFGE and plasmid analysis. beta-Lactamase genes were sought by PCR. RESULTS: Over the study period, 52 ESBL-producing Enterobacteriaceae (E-ESBL), with Escherichia coli (56%) being the most prevalent, were isolated from 24/25 adoptees at arrival in France. During follow-up, the transmission of ESBL-producing E. coli and Salmonella enterica Babelsberg between the adoptees and their adoptive family members has clearly been demonstrated for 5/22 families (23%). The mean duration of the carriage for the adopted children was 9 months (1-15 months). CTX-M-15 was the most prevalent resistance gene among the E-ESBLs (93%), while SHV-12 was found among the S. enterica Babelsberg studied. CONCLUSIONS: International travellers, transfer of patients and now adoption may contribute to the global emergence of MDR bacteria. Thus, in addition to the usual screening of adopted children for infectious diseases, additional screening for MDR bacteria should be recommended, at least for children coming from countries with a high prevalence of MDR bacteria.

[Septic arthritis after arthroscopic cruciate ligament reconstruction: in vitro comparison of the behavior of two types of interference screws towards the Staphylococcus aureus adherence]. / Arthrite septique après ligamentoplastie du pivot central sous arthroscopie : comparaison in vitro du comportement de deux types de vis d'interférence vis-à-vis de la fixation du Staphylococcus aureus.

PURPOSE OF THE STUDY: We report the results of an experimental study designed to investigate the behaviour of two types of interference screws (bioabsorbable versus titanium) in a context of Staphylococcus aureus infection. The main objective was to study one of the possible sources of failure for the treatment of acute arthritis of the knee after arthroscopic reconstruction of the cruciate ligament. MATERIAL AND METHODS: We used six interference screws made of titanium and six bioabsorbable screws (PLLA-PDLLA). All screws measured 9mmx25mm, were cannulized and sterilized. These screws were submitted to a protocol elaborated in cooperation with the bacteriologists. After contamination with a strain of S. aureus, the screws were washed four times in saline solution to eliminate germs adsorbed in the aqueous phase. The last step was trypsination to detach germs remaining fixed onto the screws and contained in the biofilms of glycocalix. A germ count was made after each step. For each screw, we determined the difference (Delta) corresponding to the number of germs really adherent to the screw. Mann-Whitney analysis was performed. RESULTS: On average, the germ count in the aqueous phase was 0.0855.10(5)/ml for the titanium screw versus 0.223.10(5)/ml for the bioabsorbable screw. The mean count of germs fixed in the biofilm (mean Delta) was 17.695+/-3.88.10(5) for the titanium screw and 45.86+/-3.61.10(5) for the bioabsorbable screw. The difference was statistically significant (p=0.0039). DISCUSSION: Our experimental results support the efficacy of abundant arthroscopic lavage in a context of infection, confirming the results of very recent studies. However, irrespective of the type of material used, bioabsorbable screws are more prone to persistent microbial adherence than titanium screws. It is hypothesized that the hydrophilic, more porous microstructure of bioabsorbable screws favors bacterial adherence. In practice, this implies that arthroscopic washout must be as abundant and as complete as possible, yet may not be sufficient to clean the entire surface of potentially contaminated screw positioned deep in a bony tunnel.

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.

[Bacteremia and pneumonia due to Yersinia enterocolitica serotype O:3 in an immunocompetent patient]. / Bactériémie et pneumopathie à Yersinia enterocolitica sérotype O:3 chez un immunocompétent.

The authors report a rare case of Yersinia enterocolitica O:3 pneumonia in an immunocompetent 70-year old man. There was no evidence of acute gastrointestinal disease. Diagnosis was confirmed by blood cultures. He responded with resolution of the infection after 21 days of therapy with a third-generation cephalosporin then by cotrimoxazole. Only 15 cases have been reported so far. Most of the patients were immunocompromised. This is the first case in France.

Decline in antibiotic resistance and changes in the serotype distribution of Streptococcus pneumoniae isolates from children with acute otitis media; a 2001-2011 survey by the French Pneumococcal Network.

Streptococcus pneumoniae is an important cause of acute otitis media (AOM). The aim of this study was to evaluate trends in antibiotic resistance and circulating serotypes of pneumococci isolated from middle ear fluid of French children with AOM during the period 2001-2011, before and after the introduction of the PCV-7 (2003) and PCV-13 (2010) vaccines. Between 2001 and 2011 the French pneumococcal surveillance network analysed the antibiotic susceptibility of 6683 S. pneumoniae isolated from children with AOM, of which 1569 were serotyped. We observed a significant overall increase in antibiotic susceptibility. Respective resistance (I+R) rates in 2001 and 2011 were 76.9% and 57.3% for penicillin, 43.0% and 29.8% for amoxicillin, and 28.6% and 13.0% for cefotaxime. We also found a marked reduction in vaccine serotypes after PCV-7 implementation, from 63.0% in 2001 to 13.2% in 2011, while the incidence of the additional six serotypes included in PCV-13 increased during the same period, with a particularly high proportion of 19A isolates. The proportion of some non-PCV-13 serotypes also increased between 2001 and 2011, especially 15A and 23A. Before PCV-7 implementation, most (70.8%) penicillin non-susceptible pneumococci belonged to PCV-7 serotypes, whereas in 2011, 56.8% of penicillin non-susceptible pneumococci belonged to serotype 19A. Between 2001 and 2011, antibiotic resistance among pneumococci responsible for AOM in France fell markedly, and PCV-7 serotypes were replaced by non-PCV-7 serotypes, especially 19A. We are continuing to assess the impact of PCV-13, introduced in France in 2010, on pneumococcal serotype circulation and antibiotic resistance.

Morphological taxonomy of the neurons of the primate striatum.

A quantitative taxonomy of primate striatal neurons was elaborated on the basis of the morphology of Golgi-impregnated neurons. Dendritic arborizations were reconstructed from serial sections and digitized in three dimensions by means of a video computer system. Topological, metrical, and geometrical parameters were measured for each neuron. Groups of neurons were isolated by using uni- and multidimensional statistical tests. A neuronal species was defined as a group of neurons characterized quantitatively by a series of nonredundant parameters, differing statistically from other groups, and appearing as a separate cluster in principal component analysis. Four neuronal species were isolated: (1) the spiny neuronal species (96% of striatal neurons) characterized by spine-free proximal dendrites (up to 31 microns) and spine-laden distal dendrites, which are more numerous, shorter, and less spiny in the human than in the monkey, (2) the leptodendritic neuronal species (2%) characterized by a small number of long, thick, smooth, and sparsely ramified dendrites, (3) the spidery neuronal species (1%) characterized by very thick dendritic stems and a large number of varicose recurrent distal processes, and (4) the microneuronal species (1%) characterized by numerous short, thin, and beaded axonlike processes. All striatal neurons give off a local axonal arborization. The size and shape of cell bodies were analyzed quantitatively in Golgi material and in materials treated for Nissl-staining, immunohistochemical demonstration of parvalbumin and histochemical demonstration of acetylcholinesterase. Only three types were distinguishable: small, round cell bodies corresponding to either spiny neurons or microneurons, medium-size elongated cell bodies, which were parvalbumin-immunoreactive and corresponded to leptodendritic neurons, and large round cell bodies, which were acetylcholinesterase-positive and corresponded to spidery neurons. Thorough analysis of previously elaborated classifications revealed that spidery neurons do not exist in rats and cats and that large cholinergic neurons in these species correspond to leptodendritic neurons. From this, it can be assumed that the dendritic domain of striatal cholinergic neurons is considerably smaller in primates than in other species. Computer simulations based on both the frequency of each neuronal species and their three-dimensional dendritic morphology revealed that the striatum consists of two intertwined dendritic lattices: a fine-grain lattice (300-600 microns) formed by the dendritic arborizations of spiny, spidery, and microneurons, and a large-grain lattice (1,200 microns) formed by the dendritic arborizations of leptodendritic neurons. This suggests that cortical information can be processed in the striatum through two different systems: a fine-grain system that would conserve the precision of the cortical input, and a large-grain system that would blur it.

Dopaminergic cell group A8 in the monkey: anatomical organization and projections to the striatum.

The first part of the study was a quantitative analysis of the distribution of A8 neurons compared with that of A9 and A10 neurons by means of tyrosine hydroxylase and calbindin-D(28K) immunohistochemistry and image analysis in monkeys. Then the striatal projection of A8 neurons was studied using retrograde and anterograde tracing methods. It was compared with that originating in cell groups A9 and A10 by performing injections of the retrograde tracer wheat germ agglutinin conjugated to horseradish peroxidase into different regions of the striatum. Ten percent of all mesencephalic dopaminergic neurons are located in cell group A8. This cell group, along with A10 and the dorsal part of A9, constitutes the dorsal tier, which accounts for 28% of mesencephalic dopaminergic neurons. Double-staining experiments showed that the neurons located in the dorsal tier were calbindin positive, whereas those from the ventral tier were not. In terms of anatomical projection, the dorsal tier mainly projects to the ventral part of the associative striatum, with preferential projections of A8 neurons to the ventrocaudal putamen, of A10 neurons to the nucleus accumbens, and of dorsal A9 neurons to both. Conversely, the main targets of the ventral tier of mesencephalic neurons (ventral part of A9) are the sensorimotor putamen and the associative caudate nucleus. In conclusion, each mesencephalic cell group projects primarily to one specific striatal region but also participates, albeit to a lesser extent, in the innervation of all the remaining striatal parts.

Dopaminergic innervation of the subthalamic nucleus in the normal state, in MPTP-treated monkeys, and in Parkinson's disease patients.

The existence of a dopaminergic innervation of the subthalamic nucleus (STN) has been demonstrated in rats but has remained controversial in primates. The aim of the present study was first to demonstrate the existence of a dopaminergic innervation of the STN in monkeys using tracing methods and then to quantify the loss of dopaminergic fibers in the parkinsonian state in monkeys and humans. Following injection of Fluoro-Gold into the STN of a vervet monkey (Cercopithecus aethiops), retrogradely labeled neurons were found to be scattered in all dopaminergic areas of the mesencephalon. Injection of biotin dextran amine into dopaminergic areas A8 and A9 of two monkeys resulted in anterogradely labeled axons located throughout the whole extent of the STN. Labeled axons that also expressed tyrosine hydroxylase (TH) were reconstructed from serial sections. Some terminal axonal arborizations had profuse branching and occupied much of the STN, and others were restricted to small portions of the nucleus. In TH-immunoreactive sections, numerous sparse, fine, and varicose TH-positive fibers were observed in the STN of normal monkeys and humans. Quantification of these TH-positive fibers revealed a 51% loss of TH-positive fibers in MPTP-intoxicated monkeys and a 65% loss in Parkinson's disease patients compared with their respective controls. These findings demonstrate the existence of a dopaminergic innervation of the STN in primates. The loss of dopaminergic innervation in MPTP-intoxicated monkeys and in Parkinson's disease patients may directly affect the activity of STN neurons and could participate in the hyperactivity of the structure.

A spatial and quantitative study of the striatopallidal connection in the monkey.

The striatopallidal connection was quantitatively analysed after three-dimensional reconstruction of biocytin-labelled striatal axons. A small striatal region gave rise to one or two elongated bands in each of the pallidal nuclei. Each band consisted of dense axonal plexuses and short axonal arborizations with few branches. Individual axons generally terminated in one band, giving a low density of varicosities on dendrites (10 per 100 microns length). This suggests that the striatopallidal connection can distribute the same striatal information to different remote pallidal regions which can in turn integrate information from different remote striatal regions. Corticostriatal information could thus be preserved or completely transformed according to the size and location of the striatal region activated.

3-D tracing of biocytin-labelled pallido-thalamic axons in the monkey.

This study presents three-dimensional tracings of axons and axonal endings of associative pallido-thalamic axons in the monkey (Macaca mulatta, M. irus). Injections of the anterograde tracer biocytin were made in the dorsal, associative region of the medial pallidum. Numerous axonal endings were observed throughout the pallidal territory of the thalamus. Four individual axons were reconstructed from serial sections and traced in three dimensions. The initial branch of each axon subdivided successively, each new branch ending in a different part of the pallidal territory. Each of the latter branches ended in a characteristic, extremely dense terminal arborization, that we called a bunch. Associative medial pallidal information may therefore be distributed throughout the pallidal territory by means of numerous branches and bunches.

A topographic study of the course of nigral axons and of the distribution of pallidal axonal endings in the centre médian-parafascicular complex of macaques.

The combination of autoradiographic and topographic methods in macaques reveals that nigral axons only cross through the medial part of the parafascicular nucleus and end more dorsally and anteriorly in the thalamus. Pallidal endings are scarce in the centre médian and essentially located in the lateral parafascicular nucleus. It is proposed here to consider the centre médian-parafascicular complex as a part of the basal ganglia.

Calbindin D-28k as a marker for the associative cortical territory of the striatum in macaque.

An immunohistochemical study was made to investigate the topographic distribution of calbindin D-28k in relation to the associative and sensorimotor cortical territories in the macaque striatum. An intense calbindin-staining was found in the caudate nucleus and ventromedial putamen, i.e., in the associative striatum. In contrast, only a weak immunoreaction was found in the dorsolateral, sensorimotor, putamen. Calbindin immunoreactivity thus appears as a specific marker for the associative striatum.

Three-dimensional morphology and distribution of pallidal axons projecting to both the lateral region of the thalamus and the central complex in primates.

This study presents a three-dimensional analysis of pallido-thalamic axons and axonal endings in the monkey (Macaca mulatta and M. irus). Injections of the anterograde tracer biocytin were made in the dorsal, associative region of the medial pallidum. Numerous axonal endings were observed within the pallidal territory of the lateral region of the thalamus and the central complex. Individual axons were reconstructed from serial sections and traced in three dimensions. Two axons made a collateral branch in the ventral part of the lateral region and ended in the central complex. In the pallidal territory of the lateral region, axons divided several times before ending in different parts of the territory in a 'bunch', a characteristic dense terminal arborization. Axonal endings in the central complex were differently organized. Our data show that associative medial pallidal information is distributed throughout the pallidal territory of the lateral region and the pars media of the central complex by means of individual axons with numerous branches and axonal endings specific to each of the two targets.

Immune complexes and autoantibodies in patients with giant cell arteritis and their relationship with autologous rosette-forming cells.

Serologic studies and lymphocyte analysis were carried out in 29 patients with giant cell arteritis (GCA). IgA-containing circulating immune complexes (CIC) were detected in 16 GCA patients with or without polymyalgia rheumatica (55%). A significant difference was demonstrated in autologous rosette-forming cells between the patients as a whole, and matched controls (8.6 +/- 2.0 vs 11.6 +/- 2.4, p less than 0.001), and also between patients with and patients without CIC (7.9 +/- 1.6 vs 9.4 +/- 2.0, p less than 0.001).

[Oropharyngeal colonization by Gram-negative bacteria in elderly hospitalized patients: incidence and risk factors]. / Colonisation oropharyngée du sujet âgé hospitalisé par des bacilles à Gram négatif: incidence et facteurs de risque.

PURPOSE: In a prospective study, we determined the predisposing conditions and the course of aerobic Gram-negative bacilli oropharyngeal colonization during the hospital stay in patients older than 70 years. METHODS: We studied 116 patients admitted in our internal medicine unit. Medical characteristics were documented for each patient. Oropharyngeal swabs were collected on the first, third, and seventh days after admission, and then once a week until discharge. Positive culture was defined as the presence of at least one colony of Gram-negative bacilli. RESULTS: We collected 306 samples from the 116 patients. The mean hospital stay was 10.6 days. Fifty patients (43%) had at least one positive oropharyngeal culture. Thirty-three patients (30%) were colonized on admission, but this prevalence decreased during hospital stay: 20% on the third day and 14% on the seventh day. In an univariate analysis, prior administration of antibiotics (P < 0.01) and use of nonsteroid anti-inflammatory drugs (P < 0.05) were associated with colonization. CONCLUSION: Aerobic Gram-negative bacilli oropharyngeal colonization was transient during the hospital stay in the elderly. The use of nonsteroidal anti-inflammatory drugs and the previous treatment with antibiotics are possible risk factors for colonization.

[Pulmonary pasteurellosis in a young patient with multiple trauma]. / Pasteurellose pulmonaire chez un jeune polytraumatisé.

A case is reported of an 18-year-old male patient who had a road traffic accident, with head and chest injuries. The patient was admitted to the surgical intensive care unit 24 h later because of an alteration of his level of consciousness. He required artificial ventilation. Five days later, he developed right-sided lower lobe pneumonia, treated with positive end-expiratory pressure. A Gram negative organism was found on bronchial brushing, but not in haemocultures. It was identified as Pasteurella multocida, sensitive to beta-lactamines, but not to amikacin. Cefotaxime, which had been started immediately after the arrival of the Gram stain result, was continued. Artificial ventilation was discontinued on day 12, and the patient left the unit on day 15. The patient was probably a P. multocida carrier, being in close contact with animals before his accident. This bacteria is often found in infected animal bite wounds. Pneumonia due to this bacteria usually occurs in immunodepressed patients, which was not the case here.