Cotrimoxazole for community-acquired urinary tract infections leads to more adverse effects than fluoroquinolones.

BACKGROUND: For several years, we applied an internal guideline for community-acquired urinary tract infections (cUTI), targeting the reduction of fluoroquinolone use (FQ) and thereby favouring cotrimoxazole (CTM) prescription. Our aim was to report adverse effects (AE) and outcome for patients presenting with cUTI and treated with these compounds. METHODS: This cohort study was based on the dashboard of our department, bringing together 28 parameters for all patients, including diagnosis, microbiological data, antibiotic therapy, AE, length of hospital stay (LHS) and outcome. We included all patients with cUTI due to Enterobacteriaeae treated with CTM or FQ, and compared these 2 groups on in-hospital AE, LHS, and unfavourable outcome defined as intensive care requirement or death. RESULTS: From June 2008 to June 2019, 640 cUTI due to Enterobacteriaeae were observed, among which 295 (46%) treated with CTM and 345 (54%) with a FQ. There were 25 AE (3.9%): 17 (5.7%) in the CTM group, and 8 (2.3%) in the FQ group (P=0.025). Adverse effects were associated with increased LHS compared to patients without AE: 11±6 vs. 7±4 days respectively, P<0.001, 11.4±6.2 days in the CTM group vs. 9.2±5.8 in the FQ group (relative LHS increase of 73.5% and 29.5%, respectively). Unfavorable outcome occurred for 1 patient (0.3%) in the CTM group, and 5 (1.4%) in the FQ group, P=0.297. CONCLUSION: Favouring cotrimoxazole for cUTI due to Enterobacteriaceae was associated compared to FQ with more AE and prolonged LHS. A cost-effectiveness analysis to validate such therapeutic strategy is warranted.

A toolkit for the management of infection or colonization by extended-spectrum beta-lactamase producing Enterobacteriaceae in Italy: implementation and outcome of a European project.

Among European countries, prevalence rates of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are particularly high in those bordering the Mediterranean. This is the case for Italy, with 26% of Escherichia coli displaying resistance to the 3rd generation cephalosporins in 2013. An ESBL-E toolkit designed to assist clinicians in managing patients harboring ESBL-E was favorably implemented in Southern France. In a context of lack of specific Italian recommendations, its extension to an adjacent region of Italy was made possible through a cross-border EU cooperation program. Italian infectious disease (ID) specialists, microbiologists, and community-based general practitioners from three districts in Liguria were offered a toolkit consisting in a warning system and detailed procedures for the management of patients harboring ESBL-E, including seeking advice from an ID specialist, and were trained during 52 video conferences by an experienced French team. Indications and trends in antimicrobial prescription were studied following implementation of the toolkit. Between November 2013 and November 2014, 476 patients were identified as harboring ESBL-E and expert advice was sought for 364 of these; all patients and/or their caregivers were advised on appropriate hygiene measures and 209/341 with documented management received antimicrobial treatment, while asymptomatic carriers (39%) were not prescribed antibiotics. The ESBL-E toolkit was well received by the healthcare staff. A specific, simple tool consisting in a care-bundle approach to manage ESBL-E carriers can restrict antimicrobial prescription to symptomatic patients while raising awareness among caregivers of the importance of seeking expert advice and implementing appropriate hygiene measures.

Efficacy and safety of clindamycin-based treatment for bone and joint infections: a cohort study.

Clindamycin has high bioavailability together with good diffusion in bone tissue and could represent an alternative antibiotic compound for the treatment of bone and joint infections (BJIs). However, data regarding the efficacy and safety of clindamycin for BJIs are limited. A monocentric cohort study based on our medical dashboard, which prospectively recorded 28 characteristics for all hospitalized patients since July 2005, was performed. BJIs were selected, and then, all mono-microbial BJI managed with clindamycin-based therapy were included. Remission was defined as the absence of clinical and/or microbiological relapse after treatment. The duration of follow-up without relapse was determined retrospectively using computerized medical records. For 10 years, 196 BJIs, of which 80 (41%) were device-associated infections, were treated with clindamycin-based therapy. The bacterial causative agent was Staphylococcus aureus in 130 cases (66%), coagulase-negative staphylococci in 29 cases (15%), streptococci in 31 cases (16%) and other bacteria in 6 cases (3%). When used in combination therapy, clindamycin was mainly paired with fluoroquinolones (31%) or rifampin (27%). The mean duration of clindamycin treatment was 7.4 ± 3.2 weeks (range, 1-24). An AE was recorded for 9 (4.5%) patients. Remission was recorded for 111 (57%) patients, with a mean duration of clinical follow-up of 28 ± 24 months. Treatment failure occurred in 22 (11%) patients, 50 patients (25%) were lost to follow-up, and 8 (4%) required long-term suppressive therapy. Among the assessable patients, clindamycin-based therapy was efficient in 111/133 cases (83%) and thus represents a reliable and safe alternative treatment option.

Medical table: A major tool for antimicrobial stewardship policy.

Infectious diseases are unpredictable, with heterogeneous clinical presentations, diverse pathogens, and various susceptibility rates to anti-infective agents. These features lead to a wide variety of clinical practices, which in turn strongly limits their evaluation. We have been using a medical table since 2005 to monitor the medical activity in our department. The observation of heterogeneous therapeutic practices led to drafting up our own antibiotic guidelines and to implementing a continuous evaluation of their observance and impact on morbidity and mortality associated with infectious diseases, including adverse effects of antibiotics, duration of hospital stay, use of intensive care, and deaths. The 10-year analysis of medical practices using the medical table is based on more than 10,000 hospitalizations. It shows simplified antibiotic therapies and a reduction in infection-related morbidity and mortality. The medical table is a major tool for antimicrobial stewardship, leading to constant benefits for patients.

Antimicrobial stewardship policy: time to revisit the strategy?

Recent data indicate that both the overall numbers of antibiotic prescription and the frequency of multidrug-resistant bacteria are increasing significantly. These threatening features are observed, despite national antimicrobial stewardship (AMS) policies aimed at decreasing antibiotic use. AMS should also focus on the initial steps leading to antibiotic prescription. Physicians and their patients should benefit from the structured clinical pathways, the latter being adapted to regional epidemiological data and resources. Continuous evaluation of these predefined clinical paths through a computerized medical dashboard will allow a critical review and finally the optimization of medical practices. These innovative behavioural approaches for clinicians will supply precise information on the relationship among the diagnosis, therapeutics and outcome. This changing environment will carry out the adapted therapeutic procedures, and appropriate antibiotic use will inherently improve.

The impact of bacteremia on the outcome of bone infections.

UNLABELLED: We have used a medical database to analyze our activity since 2005. We observed a frequent association between bone and joint infection (BI) and bacteremia. Our aim was to characterize patients with BI and bacteremia, and focus on the outcome. PATIENTS AND METHOD: Our database includes the prospective recording of 28 characteristics of all hospitalized patients, including diagnosis, comorbid conditions, microbiological data, therapy, and outcome. We selected patients presenting with BI in this database, from July 2005 to December 2012. Fever before blood culture was retrospectively documented from the patient's chart. Chronic BI was defined as a disease lasting more than 1 month. An unfavorable outcome was defined by the need for intensive care or death. RESULTS: Six hundred and thirty-two patients presented with BI and 125 with bacteremia (19.8%). We used a stepwise logistic regression analysis and determined that bacteremia was associated with vertebral osteomyelitis, OR, 3.97, P<0.001; alcohol abuse, OR, 2.51, P=0.010; fever, OR, 2.43, P<0.001; neurological and/or psychiatric diseases, OR, 2.41, P ≤ 0.001; and Staphylococcus aureus infection, OR, 2.32, P<0.001. The outcome was unfavorable in 23 cases (3.6%), associated with bacteremia, OR, 8.00, P<0.001, age> 60 years, OR, 4.78, P=0.018, and S. aureus infection, OR, 3.96, P=0.010. No single comorbid condition was significantly associated with an unfavorable outcome. CONCLUSION: Bacteremia occurred in nearly 20% of the patients presenting with BI, and was associated with identifiable comorbid conditions; it was the main risk factor for an unfavorable outcome.

Antibiotics-related adverse events in the infectious diseases department of a French teaching hospital: a prospective study.

Antibiotics are a significant cause of adverse events (AE), but few studies have focused on prescriptions in hospitalized patients. In infectious diseases departments, the high frequency and diversity of antibiotics prescribed makes AE post-marketing monitoring easier. The aim of our study was to assess the incidence and type of AE in the infectious diseases department of a French teaching tertiary-care hospital. The main characteristics of each hospitalization, including all antibiotics prescribed and any significant AE were recorded prospectively in the medical dashboard of the department. We included all patients having suffered an AE due to systemic antibiotics between January 2008 and March 2011. Among the 3963 hospitalized patients, 2682 (68%) received an antibiotic and 151/2682 (5.6%) suffered an AE. Fifty-two (34%) AE were gastrointestinal disorders, 32 (21%) dermatological, 20 (13%) hepatobiliary, 16 (11%) renal and urinary disorders, 13 (9%) neurological and 11 (7%) blood disorders. Rifampin, fosfomycin, cotrimoxazole and linezolid were the leading causes of AE. Sixty-two percent of the antibiotics causing an AE were stopped and 38% were continued (including 11% with a dose modification). Patients suffering from AE had an increased length of stay (18 vs 10 days, P < 0.001). Our data could help choosing the safest antibiotic when several options are possible.

Altered visuo-motor behavior during inactivation of the caudal fastigial nucleus in the cat.

It is known that the medio-posterior cerebellar lobules VI/VII of the vermis and caudal part of the fastigial nucleus (cFN) are involved in the control of saccadic displacements of the visual axis in space (gaze). We have recently shown in the head-unrestrained cat that inactivation of the cFN severely impairs the accuracy of orienting gaze shifts toward visual targets by altering the amplitude of both eye and head components. In the present paper, we report additional data that indicate that the deficits induced by cFN inactivation are not restricted to saccadic gaze shifts but extend to the forward reaching movement of the whole body toward a visual target. Indeed, the path followed by the animal walking toward a visible food target was systematically curved toward the inactivated side. This deficit could largely be accounted for by an angular bias in the heading direction used by the animal to reach the target. These data suggest that pharmacological inactivation of the cFN leads to a general deficit in spatial orientation.

Absence of vestibular habituation of the vestibulo-ocular reflex in the vertical plane in the cat.

The effect of exposure to repeated angular velocity steps about the earth-vertical axis on the vertical vestibulo-ocular reflex (VOR) during onside pitch rotation was investigated in normal cats. By contrast with the VOR in the horizontal plane, the amplitude and duration of the vertical VOR did not progressively decrease throughout the repetition of velocity steps alternated in both directions. Instead, the amplitude of VOR decreased by about 40% during the very first trials in naive cats and then stayed unchanged with repeated stimuli. Habituation of the amplitude of the vertical VOR was observed when the velocity steps were always directed in the same direction. However, the duration of the vertical VOR did not show any signs of habituation. The habituation of the amplitude of the vertical VOR during unidirectional training was due to the progressive development of an initial inhibition of the VOR. This initial inhibition appeared much earlier during the bidirectional protocol, and was presumably responsible for the larger reduction in VOR amplitude observed during the very first session. These results support the model of two distinct mechanisms for VOR habituation, one producing an increasing inhibition of nystagmus, and the other depressing the response duration, and suggest that only the first mechanism is generated during repeated stimulation in the vertical plane. The low-frequency information provided by the velocity storage mechanism during onside pitch rotation, when the otoliths are positioned so they do not signal head tilt relative to gravity, could prevent a decrease in the overall response by the second mechanism.

Acetylcholinesterase activity changes in medial vestibular complex after hemilabyrinthectomy in the rat.

Acetylcholinesterase (AchE) activity was studied in pigmented rats 6 h to 1 y after hemilabyrinthectomy. A strong reduction of this activity was localized in the rostrocaudal extent of both the prepositus hypoglossi nucleus and the medial vestibular nucleus (that is, medial vestibular complex: VCm) ipsilateral to the lesion 6 h after the lesion. This deficit persisted within some areas dispersed throughout this complex 3 w and 1 y postoperatively. This result supports the hypothesis that the asymmetry of AchE activity in VCm could be necessary for vestibular compensation and provides an additional model for functional plasticity in the central nervous system.

Rapid compensation of horizontal optokinetic nystagmus in hemilabyrinthectomized rats: a fast return to symmetry.

In the rat, after unilateral labyrinthectomy the loss of unit responses in the deafferented ipsilateral vestibular nucleus should lead to a complete postlesional asymmetry in H-OKN. The compensation process of this oculomotor deficit were recorded by means of a search coli technique using amplitude detection in 30 pigmented rats, 8 animals as control and 22 submitted to left hemilabyrinthectomy. Recording sessions were performed from day 1 to 8 after the lesion. Velocity steps of visual stimulation were delivered in clockwise (CW) and counterclockwise (CCW) directions at velocities from 2 to 40 degrees/s. The H-OKN was not observable on postlesional day 2. It reappeared asymmetrical on day 2 with depressed responses to CW stimulation while the response to the CCW stimulation were almost as large as in intact animal. This asymmetry was quantified by the gain values (eye velocity/stimulus velocity) of the nystagmic responses which were, at 5 degrees/s of stimulus velocity, 0.37 for CW stimulation and almost twice as large, 0.72 for CCW stimulation. Later this asymmetry was consistently reduced by a progressive increase of the CW responses and a parallel decrease of the CCW. This process led to the responses to reach almost symmetrical values on day 8 with a gain of 0.52 and 0.63 for CW and CCW responses respectively at the same stimulus velocity. However the gain of intact animals was never attained. The initial eye velocity was symmetrically altered on day 2 and remained unchanged until postlesional day 8. These results demonstrate that the deficit appeared to be compensated more by a restoration of a symmetry than by a restitution of a gain of responses equivalent to that of an intact animal.

Anatomical segregation of different adaptative processes within the vestibulocerebellum of the cat.

Bilateral surgical lesions of the flocculus or the nodulo-uvular lobes were performed in the cat. Effects of these lesions on optokinetic and optokinetic afternystagmus OKAN), vestibulo-ocular reflex (VOR), visual suppression, and adaptation and habituation of VOR were studied using an identical experimental protocol. After flocculectomy, all these functions were impaired, except for habituation. Long-term postoperative recordings only revealed a recovery of the suppression of VOR, suggesting a limited contribution of the flocculus to this function. After nodulo-uvulectomy, only habituation and OKAN were modified. When the lesion was restricted to part of the uvula, OKAN duration was decreased. For other lesions involving the uvula together with the nodulus and/or the lobules VII-VIII,OKAN duration was increased. Habituation was lost after destruction of the nodulo-uvular lobes. When this latter structure was damaged, the retention component of habituation was selectively impaired, sparing the acquisition. Additional lesions outside the vestibulocerebellum appeared necessary to suppress the two components. Comparison of results obtained after flocculectomy and after nodulouvulectomy confirms and extends to non-primate species the concept of a "differential control" of adaptation and habituation by distinct vestibulocerebellar structures.

Longterm impairment of cat optokinetic nystagmus following visual cortical lesions.

Binocular and monocular gain of optokinetic nystagmus (OKN), OKN dynamics, vestibulo-ocular reflex (VOR) and VOR adaptation were measured in 5 normal cats and in 5 cats which underwent bilateral visual cortical lesions involving the 17-18 complex at least 4 months before testing. We observed longterm deficits after bilateral lesions involving area 17 and variable parts of area 18 but failed to observe deficits after 18-19 lesions. These deficits were limited to the OKN gain and the build-up time constant of OKN; the VOR and the optokinetic after-nystagmus (OKAN) time constant were within normal limits. Our results suggest that areas 17-18 operate in parallel to control the encoding of retinal slip velocity at the level of the nucleus of the optic tract (NOT) and the accessory optic system (AOS), which are known to represent the initial stage of the optokinetic pathways.

Optokinetic nystagmus in the ferret: including selected comparisons with the cat.

The aim of this study was to evaluate the functional significance of similarities observed in the anatomy and the physiology of cat and ferret visual systems. Optokinetic nystagmus (OKN) in response to movement of the entire visual field, and optokinetic after nystagmus (OKAN) were measured in 8 ferrets with binocular stimulation. A shift of the beating field in the same direction as the fast phase of eye movements was observed both in ferret and cat. The absence of a fast rise in slow phase velocity (SPV) and similarities in the time constant to reach the steady state OKN gain, using step velocity stimuli are noted. As in the cat, primary OKAN was observed with a gradual decrease in its SPV. Following termination of stimulation, no sudden fall in SPV was noted for either species. However, for the ferret, the decrease was more rapid. With monocular stimulation, small differences were observed in OKN gain when responses to temporonasal and nasotemporal directions of the stimulus were compared in the two species. In contrast, the ferret displays a OKN gain which is approximatively twice that of the cat at stimulus velocities of 100 degrees/sec. Even at 200 degrees/sec., visual movement still induces a discernable OKN response (gain .0.07). Secondary OKAN, always present in the cat, was observed in only 43% of ferret records. Taken together with other considerations, these findings recommend the ferret as an alternative to the cat for the study of OKN and of other visuo-motor capacities in carnivores.

Horizontal optokinetic responses under stroboscopic illumination in cat, monkey and man.

The horizontal optokinetic reflex (OKN) was studied in cat, monkey and man under conditions of steady or stroboscopic illumination. In all species, there was an abrupt decrease in OKN gain for a given spatial displacement of the stimulus between two consecutive stroboscopic flashes. The upper limit of spatial displacement which preserved optimal OKN gain was independent of stimulus velocity and flash frequency. The value of this limit differed in the three species studied. In the cat, OKN gain was affected when the spatial displacement between two stimuli exceeded 0.55 degrees of visual angle. In monkey and man, these limits were 1.48 degrees and 2.87 degrees, respectively. When human subjects were asked to volontary track the stimulus, the limit value reached 4.3 degrees. This result is discussed in the context of the evolution of the smooth pursuit system and its contribution to optokinetic response.

[The French Society of EEG and Clinical Neurophysiology is 40 years old]. / La Société d'EEG et de Neurophysiologie clinique de Langue française a 40 ans.

The historical reminder of the foundation of the French EEG Society and the changes which have occurred during its operation show the worry of the Society for a better efficiency all along this last fourty years. A general survey of the scientific activities disclose the contribution of the society in the papers first published in the Revue Neurologique, and, after 1971, in the Revue d'EEG et de Neurophysiologie clinique de Langue française. The French participation in other clinical neurophysiological or scientific meetings in France and abroad is underlined by the important role it has played in the life of the International Federation for EEG Societies. Training of specialized doctors and technicians in the domain of the functional exploration of the nervous system has been a standing preoccupation of the Society, with the teaching of the so-called "Attestation d'EEG" in French universities and the training of technical personnel in specialized schools.

Cross-coupled effects of repeated vestibular and optokinetic stimulations on the dynamics of the vestibulo-ocular and optokinetic reflexes in the cat.

Cats were submitted to repeated step stimulations either vestibular or optokinetic. Regardless of which of the two stimuli was used, dynamic modifications were observed in both vestibulo-ocular response and optokinetic after-nystagmus (OKAN). The progressive changes in post-rotational nystagmus and OKAN were quantified by measuring the duration of their primary phase. A parallel evolution of these two parameters was found. When repeated unidirectional vestibular stimulations were used, the same asymmetry was induced in both vestibuloocular responses and OKAN. These results support the hypothesis that the vestibulo-ocular and the optokinetic reflex share a common velocity storage mechanism, although alternative hypotheses cannot be excluded.