Factors associated with daptomycin consumption in French hospitals between 2019 and 2020: A nationwide surveillance study.

OBJECTIVES: This study aimed to investigate factors associated with daptomycin consumption in French healthcare facilities (HCF) between 2019 and 2020. METHODS: Antibiotic consumption expressed as number of defined daily doses (DDD) per 1,000 patient-days (PD) and antimicrobial resistance (AMR) expressed as incidence densities per 1,000PD were extracted each year from the nationwide surveillance network run by the SPARES project (Surveillance and Prevention of Antimicrobial RESistance in hospitals), collecting data at ward level among voluntary HCFs using standardized methodology and webtool. All HCF participating both in 2019 and 2020 were included. A multivariable linear regression was fitted. RESULTS: Among 622 HCFs, we analyzed daptomycin consumption and AMR data in 1,637 clinical wards. Incidence densities of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCNS) were the highest in intensive care unit wards (0.54 and 6.83 respectively in 2020). On the most adjusted model, the year 2020 was correlated with a higher daptomycin consumption (1.53; p = 0.01). A greater number of inpatient beds (0.01; p < 0.001), the presence of orthopedic surgery activity in the HCF (1.66; p < 0.02), MRSA (4.38; p < 0.001) and MRCNS (0.61; p < 0.001) incidence densities were associated with a higher daptomycin use. The final model explained 18% of the observed variance. CONCLUSIONS: This study showed that daptomycin consumption was correlated to MRSA and MRCNS incidence densities, to the year 2020 and to non-modifiable HCF-related factors. Prevention of coagulase-negative staphylococci infections should be considered by antimicrobial stewardship teams when daptomycin use is going up in HCF.

Early rehabilitation management strategy for septic arthritis of the knee.

OBJECTIVES: Early rehabilitation management of septic arthritis in the native knee is not standardized. In this context, it is necessary to develop and validate an early rehabilitation strategy. MATERIEL AND METHODS: Based on the formalized HAS consensus method, a 4-phase rehabilitation strategy has been developed: recovery of joint amplitudes, muscle recovery without resistance, recovery with technical aid (crutches, canes), continuation of the rehabilitation (pursuit of muscle, articular, proprioceptive and endurance recovery). RESULTS: It was submitted to the opinion of multidisciplinary experts (PMR, general practitioner, rheumatologist, infectiologist, orthopedic surgeon, physiotherapist). Nearly 80% of the items were directly validated, with only five items scoring less than 5/10. Modifications were made in order to obtain a final version of the protocol. CONCLUSION: Use of a rigorous methodology enabled a consensual strategy for early rehabilitation management to be developed. Prospective validation of this strategy is needed to confirm its feasibility and effectiveness.

Educating patients about the benefits of physical activity and exercise for their hip and knee osteoarthritis. Systematic literature review.

OBJECTIVES: Highlight the role of patient education about physical activity and exercise in the treatment of hip and knee osteoarthritis (OA). METHODS: Systematic literature review from the Cochrane Library, PubMed and Wiley Online Library databases. A total of 125 items were identified, including 11 recommendations from learned societies interested in OA and 45 randomized controlled trials addressing treatment education and activity/exercise for the treatment of hip and knee osteoarthritis. RESULTS: In the end, 13 randomized controlled trials and 8 recommendations were reviewed (1b level of evidence). Based on the analysis, it was clear that education, exercise and weight loss are the pillars of non-pharmacological treatments. These treatments have proven to be effective but require changes in patient behaviour that are difficult to obtain. Exercise and weight loss improve function and reduce pain. Education potentiates compliance to exercise and weight loss programs, thereby improving their long-term benefits. Cost efficiency studies have found a reduction in medical visits and healthcare costs after 12 months because of self-management programs. CONCLUSION: Among non-surgical treatment options for hip and knee osteoarthritis, the most recent guidelines focus on non-pharmacological treatment. Self-management for general physical activity and exercise has a critical role. Programs must be personalized and adjusted to the patient's phenotype. This development should help every healthcare professional adapt the care they propose to each patient. Registration number for the systematic review: CRD42015032346.

The haemosporidian parasites of bats with description of Sprattiella alecto gen. nov., sp. nov.

Four species of Haemoproteidae were found in Pteropus alecto Temminck, 1837 in Queensland, Australia: i) Johnsprentia copemani, Landau et al., 2012; ii) Sprattiella alecto gen. nov., sp. nov., characterised by schizonts in the renal vessels; iii) Hepatocystis levinei, Landau et al., 1985, originally described from Pteropus poliocephalus Temminck, 1825 and, experimentally from Culicoides nubeculosus and found in this new host and for which features of the hepatic schizonts are reported; iv) gametocytes of Hepatocystis sp. which are illustrated but cannot be assigned to a known species. A tentative interpretation of phylogenetic characters of haemosporidians of bats is provided from the morphology of the gametocytes and localisation of the tissue stages with respect to recent data on the phylogeny of bats.

Comparison of two in vitro methods to evaluate the water resistance of sunscreens.

For a long time, the water resistance of sunscreens has been determined in vivo, according to Colipa's (Comité de Liaison des Industries de la Parfumerie) procedure. This method is not so ethical as healthy volunteers are irradiated, and can be replaced by an in vitro method which is easy and quick to perform. The objective of this work was to correlate the experimental device proposed by Choquenet et al. and the dissolutest (Sotax AT6). This equipment is used in the pharmaceutical industry to control the tablets. The experimental conditions have been fixed to correlate the results obtained with both methods. The stirring speed for the dissolutest was fixed at 75 rpm, which is the speed value recommended by the European Pharmacopeia to study the dissolution over time of tablets.

The sub-genera of avian Plasmodium.

The study of the morphology of a species of Plasmodium is difficult because these organisms have relatively few characters. The size of the schizont, for example, which is easy to assess is important at the specific level but is not always of great phylogenetic significance. Factors reflecting the parasite's metabolism provide more important evidence. Thus the position of the parasite within the host red cell (attachment to the host nucleus or its membrane, at one end or aligned with it) has been shown to be constant for a given species. Another structure of essential significance that is often ignored is a globule, usually refringent in nature, that was first decribed in Plasmodium vaoughani Novy & MacNeal, 1904 and that we consider to be characteristic of the subgenus Novyella. Species without this structure, previously classified in this sub-genus, are now included in the new sub-genus Papernaia n. sg.

Development of bisphosphonates controlled delivery systems for bone implantation: influence of the formulation and process used on in vitro release.

The present study investigates the development of controlled drug delivery devices by association of bisphosphonates (BPs) with calcium-deficient apatite (CDA) to obtain a prolonged drug delivery. In a first part, we studied the microencapsulation of methylene bisphosphonic acid, our model of BPs, in biodegradable PLGA by the double emulsion (w/o/w) solvent evaporation/extraction process. Secondly, we associated BPs, either in a free form or microencapsulated, with calcium phosphate biomaterials. The association of free BPs with CDA was performed by isostatic compression at 80 MPa and we tested the interest of adding a binder, HPMC, in the formulation to reinforce the association. In parallel, microparticles were associated with calcium-deficient apatite, either by simple mixture or by isostatic compression. To compare the different formulations, in vitro dissolution studies were performed. All the formulations tested appear to be efficient to produce BPs loaded biomaterials able to deliver the drug slowly and at a constant rate. The slowest release rate (2.7% in 14 days) was obtained with the blend of microencapsulated BPs with CDA.

[Probable speciations by "host-vector 'fidelity'": 14 species of Plasmodium from magpies]. / Fidélisation du couple hôte-vecteur facteur probable de spéciation: 14 espèces de Plasmodium de la Pie.

33 Magpies resident in two parks close to Paris were investigated for the presence of Plasmodium parasites. The majority of the birds were found to be infected with multiple parasite species. A total of 14 species were observed, and of these 10 were novel and consequently described, and two could not be assigned with confidence. It is hypothesized that the unexpected abundance of species is due to a phenomenon which we term "host-vector 'fidelisation'". Indeed, the combination of the eco-biological characteristics of the host (mating pairs in contiguous, but strictly defined territories) with those of the vector (numerous Aedes species with distinct behavior), would generate fragmentation of the niches. This type of isolation overlays others known for parasitic populations (geographical, circadian, microlocalisations), leading to the formation of independent host-parasite niches which in turn lead to speciation.

Eimeria (Coccidia: Eimeridea) of hares in France: description of new taxa.

The oocysts of coccidian of the genus Eimeria were sought in the caecal contents of 46 Lepus granatensis and 18 L. europaeus captured in France. Parasites were found in 34 of the hares. Parasite load was mainly very low. However, species diversity was considerable. 21 species or subspecies were identified, of which 13 species and two subspecies were not previously described. Three of the taxa, E. robertsoni, E. semisculpta and E. townsendi, previously identified on numerous occasions in western Europe and, corresponding to forms or variants created before 1960 that have been subsequently elevated to a specific level, appear to be invalid. Indeed, the parasite descriptions from the material used to effect this modification do not correspond to the original descriptions. A stable equilibrium, as generally observed in the case of many congeneric species co-infection of the same host, was not observed in the hares. This has been attributed to the solitary habits of the host and of the probable polyphyletic nature of the genus Eimeria. Paleontological data for the Leporidae indicate that rabbit parasites are derived from those of the hare.

Action of adrenalin on the circulation of the murine Plasmodium developing stages, in different blood compartments.

Adrenalin was used to investigate in vivo the circulation of the different stages of rodent Plasmodium present in the blood. A single dose of adrenalin injected to mice infected with P. yoelii resulted immediately in i) a diminution of the parasitaemia of approximately 50% in the peripheral large vessels (estimated in tail blood films), as well as in the capillaries (estimated in smears of blood collected from a fed Anopheles), and ii) an increased parasitaemia in blood collected by cardiac puncture from the right heart. The numbers of young stages of P. yoelii in the peripheral blood were initially somewhat reduced but, unexpectedly, midterm trophozoites were preferentially expelled from the peripheral blood into major organs like the heart. With P. vinckei, parasitaemia decreased only when midterm trophozoites predominated, and with P. chabaudi no effect was observed at any time. We propose that midterm trophozoites, by their increased surface area, as compared to rings, and their flexibility which contrasts with the rigid schizonts, are particularly susceptible to haemodynamic perturbations.

Coccidiosis of the wild rabbit (Oryctolagus cuniculus) in France.

In 1998-1999 a survey of coccidiosis in wild rabbits was carried out in six different localities in France. About five individuals were caught monthly in each locality and a total of 254 wild rabbits was examined. Ten species of Coccidio were identified: Eimeria perforans, E. flavescens, E. piriformis, E. exigua, E. media, E. magna, E. coecicola, E. stiedai, E. roobroucki, E. intestinalis. Intensity of infection in young individuals was higher than in adults. Intensity was highest in winter but, as there are no young rabbits in winter, in young individuals it was higher in spring and autumn than in summer. Intensities were higher in the northern rather than in southern localities. Ranking of prevalence was remarkably stable, in contrast to the variability of the parasitic load. The equilibrium between congeneric species of rabbit coccidia (stable prevalence rank, variable parasitic load) is thought to be probably the consequence of the opportunistic feeding habits of rabbits.

Taxonomic status and re-description of Plasmodium relictum (Grassi et Feletti, 1891), Plasmodium maior Raffaele, 1931, and description of P. bigueti n. sp. in sparrows.

The first accurate re-description of Plasmodium relictum (Grassi et Feletti, 1891) in its type host was provided by Raffaele in 1931, and the name relictum should thus refer to this work. In his article, Raffaele noted the presence of an associated but distinct species, P. maior. The work of Raffaele has since remained overlooked, and the taxon relictum has been applied rather loosely to parasites found in numerous birds of diverse geographic origin. Examination of Passer domesticus specimens collected in France has confirmed the presence of the two species above, and further revealed that two other species can also be found in these birds. P. bigueti n. sp. is described here, whereas the other Plasmodium sp. was not found in sufficient numbers to allow characterisation.

Parasitic pattern of rodent Plasmodium in blood from mouse tail and from Anopheles blood meal.

During the course of the infection of mice by rodent malaria parasites (P. yoelii yoelii, P. vinckei petteri, and P. chabaudi chabaudi) the parasitic pattern in the blood smears differed according to the site of sampling: mosquito blood meal (usually actively sucked from capillaries) or mouse tail (issued from larger vessels). There were fewer old trophozoites and mature schizonts, and more immature schizonts, in the mosquito blood meal than in the tail blood of mice. It is suggested that the erythrocyte containing a schizont becomes less rigid when merozoites formation begins. The greater abundance in the mosquito blood meal of the gametocytes infective stage (0-I for P. yoelii, II for P. vinckei), previously shown, could be due to a particular flexibility of this stage, a character progressively selected.

Variation in murid Plasmodium desequestration and its modulation by stress and pentoxifylline.

Changes in the parasitaemia and the characteristics of parasitic infection for three species of rodent Plasmodium (P. chabaudi chabaudi, P. vinckei petteri and P. yoelii yoelii) were investigated under conditions of stress and after treatment with pentoxifylline (POF), a drug that increases red blood cell deformability and causes peripheral vasodilatation. The results indicated that under stress, late parasite stages became less abundant in the tail blood of mice. These changes might be the consequence of parasite sequestration. Attempts to assess sequestration intensity were made by measuring the release rate (RR) of late stages for 10,000 red blood cells. The RR is given by the product of the parasitaemia (P) by the percentage of old trophozoites (OT) and schizonts (S) in the peripheral blood: RR = P(%OT + %S) . With all three species, RR decreased considerably within 5 min following the manipulation of the mice. Injections of POF had the opposite effect. POF had a protective effect against infection by P.v. petteri, causing a delay of 48 h in the development of infection and a higher survival rate in treated mice.

New Pudicinae (Trichostrongylina, Heligmosomoidea) coparasites of Proechimys longicaudatus (Caviomorpha) from Bolivia. I--Description of Pudica ginsburgi n. sp. and Heligmostrongylus chiarae n. sp.

Two new Pudicinae (Trichostrongylina, Heligmosomoidea, Heligmonellidae) coparasites of Proechimys longicaudatus (Caviomorph rodent) from Bolivia are described: Pudica ginsburgi n. sp. is differentiated from all the other species of the genus by the great length of the spicules and of the vestibule and by a different ratio of the length of the spicules on the length of the body. Heligmostrongylus chiarae n. sp. has very developed rays 4, strongly divergent from rays 5 as occurs in three other species, H. almeidai (Durette-Desset & Tcheprakoff, 1969), a parasite of Trichomys apereoides (= Cercomys cunicularius) from Brazil, H. squamastrongylus (Travassos, 1937), a parasite of Proechimys oris from Brazil and H. proechimysi Durette-Desset, 1970, a parasite of Proechimys semispinosus from Columbia. The specimens from Bolivia are differentiated from the three species by the division of the dorsal ray (anterior half versus posterior half) and by a different ratio of the length of the spicules on the length of the body.

Short-term effect of chloroquine on the infectivity of Plasmodium chabaudi gametocytes.

The short-term enhancing effect of chloroquine on gametocyte infectivity was investigated with Plasmodium chabaudi chabaudi, a synchronous parasite which is highly sensitive to chloroquine. In comparison with control groups, oocyst numbers increased in mosquitoes fed on mice 12 hours after the injection of 5 mg/kg chloroquine (180% of controls) although it was not statistically significant. No effect was seen with 1 mg/kg chloroquine. The authors interpretation is that chloroquine impaired the schizogony, thus reducing also the release of toxic material of parasite origin which blocks gametocytes infectivity. Results of similar experiments with other rodent species of Plasmodium are compared and discussed in relation with the chronobiological characteristics of these parasites.

The effects of subcurative doses of chloroquine on Plasmodium vinckei petteri gametocytes and on their infectivity to mosquitoes.

The effects of subcurative doses of chloroquine on rodent and human Plasmodium transmission to the mosquito have been studied by several authors who showed a short-term (12 h) enhancement of gametocyte infectivity by the drug, restricted to chloroquine-resistant strains, and a long term (4-6 days) enhancement of gametocytogenesis of chloroquine-sensitive strains of Plasmodium chabaudi. We investigated both short- and long-term effects of chloroquine on Plasmodium vinckei petteri, a chloroquine-sensitive rodent Plasmodium strain. Chloroquine treatment reduced the index of gametocytogenesis to 73% (5 mg/kg) and 55% (2.5 mg/kg) of controls, on day 6 post-infection (p.i.). The reduction was statistically significant with 5 mg/kg chloroquine. However, the reduction of gametocyte numbers did not affect the transmission capabilities of the strain. Our experiments showed that doses of 1 mg/kg chloroquine had no effect on the oocyst counts, 12 h post-administration to mice. A statistically non-significant 61% reduction of oocyst numbers was observed in mosquitoes fed on mice treated with 5 mg/kg chloroquine. The effect of 5 mg/kg chloroquine administration on the infectivity of gametocytes to mosquitoes fed 1 h post-treatment was also investigated. An overall 41% reduction of oocyst numbers was observed. This immediate effect was statistically significant in 73% of the mice. These results are consistent with the hypothesis that the short-term enhancing effect of chloroquine on transmission is restricted to the drug-resistant strains of Plasmodium.

A cladistic analysis of the Trichostrongyloidea (Nematoda).

A morphologically based cladistic analysis of 40 genera included within the Trichostrongyloidea (Amidostomatidae, Dromaeostrongylidae and Trichostrongylidae) is proposed. Two genera were used as outgroups, one from the Strongylina and the other from the Ancylostomatina. Seven genera do not appear in the matrix because some significant morphological characters remain unknown for these genera. Nonetheless, except for Moguranema which is excluded as incertae sedis, a likely systematic position could be assigned to them based on the morphological characters that are known. The classification which best fits the consensus tree is composed of three families. In adding the genera not included in the tree, we obtain: (i) Trichostrongylidae with three sub-families, Amidostomatinae (four genera), Filarinematinae (three genera) and Trichostrongylinae (five genera); (ii) Haemonchidae with two sub-families: Ostertagiinae (eight genera) and Haemonchinae (five genera); (iii) Cooperiidae with three sub-families: Libyostrongylinae (five genera), Obeliscoidinae n. subfam. (five genera) and Cooperiinae (ten genera). Dromaeostrongylus and Ortleppstrongylus, whose females have a caudal spine, are excluded from the Trichostrongyloidea and are placed in the Molineoidea. The hypotheses relating to the evolutionary history of the Trichostrongyloidea are: the origin of the superfamily could have occurred during the upper Cretaceous period. The two most ancient sub-families (Amidostomatinae and Filarinematinae) would be of Gwondwanan origin and evolved during the Paleocene period within Neotropical aquatic birds and within the Australian marsupials. The Trichostrongylinae would have arisen during the Eocene period within birds and then adapted to diverse archaic mammals in the Neotropical region on one hand and in the Nearctic region, on the other hand and lastly adapted to the Lagomorpha and subsequently to the Ruminantia. In both families originating from the Trichostrongylidae, the adaptation to the Lagomorpha may have taken place during the Oligocene but in a different way. In the Haemonchidae, the Ostertagiinae may have passed directly from the Neartic region to Europe. In the Cooperiidae, the adaptation to Lagomorpha may have occurred either within the Libyostrongylinae which may have remained in the Ethiopian region since the Paleocene, or, more likely, by the passage of the Obeliscoidinae from the Nearctic region to the Asian, through the Bering strait. In all cases, the adaptation of the Trichostrongyloidea of Lagomorpha to Ruminants apparently took place during the Miocene, mainly in the Palearctic and the Ethiopian regions.

Final stage of maturation of the erythrocytic schizonts of rodent Plasmodium in the lungs.

Schizonts of all rodent Plasmodium studied (Plasmodium yoelii, P. chabaudi, P. vinckei) show a characteristic morphology when they are completely mature: rounded or slightly elongate merozoites, completely detached from the pigment mass. At this stage, they are localized principally in the spleen and the lungs but, in impression smears of these organs they show two different aspects. In the spleen, schizonts are either inside the host erythrocyte or extraglobular but still close to a pigment mass; free merozoites are rare. In the lungs, on the contrary, merozoites are often free and dispersed; electron microscopy showed them to lie against the endothelium. Work by physiologists has shown the blood circulation in the alveoli to be much slowed down. Free merozoites, lined against the endothelium of relatively rigid capillaries, are in the best possible conditions to make contact with the intact red blood cells. Lungs appear to be the privileged site for the invasion of erythrocytes by the merozoites.

Survival of rodent malaria merozoites in the lymphatic network: potential role in chronicity of the infection.

Experiments performed during the last few years, lead us to hypothesise the existence of latent asexual forms of murine Plasmodium. In the present report we examined the organs of infected animals and describe novel structures, which we call merophores, containing merozoites which have resisted lysis seen with other asexual stage parasites. We propose that these merozoites represent a latent form of the parasite. Merophores were also found in the lymphatic circulation, and were demonstrated by subinoculation to have retained their viability. Depending on the parasite species two types of merophores were observed. For P. yoelii nigeriensis merophore sacks, with the latent merozoites found inside vesicles, were usually observed. Merophore leucocytes, where latent merozoites dispersed in the cytoplasm of macrophages or neutrophils, were solely seen with P. vinckei petteri. Both structures were seen in P. chabaudi chabaudi infections. Merophores were found in lymph nodes of rodents after the asexual parasitaemia had apparently subsided. They were formed soon after schizogony, principally in the spleen, either by pitting or by macrophage phagocytosis. Merophore numbers appeared to be proportional to the number of maturing schizonts. We propose that merophore formation and their circulation in the lymphatics play an important role in the pattern of recrudescences and chronicity of rodent malaria infections. It is further suggested that the lymphatic network, a privileged pathway for many parasites, might play a similar role in human malaria infections.