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.

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.

[1997-2007, 10 years of monitoring the evolution of resistance of Streptococcus pneumoniae to antibiotics in the region Centre; review of the Pneumococcus network]. / 1997-2007, dix ans de suivi de l'évolution de la résistance de Streptococcus pneumoniae aux antibiotiques en région Centre; bilan de l'observatoire du pneumocoque.

Regional pneumococcal observatories in region Centre, created in 1997, participate with the others pneumococcal observatories alongside the National Reference Center for Pneumococci and the Institut de Veille Sanitaire at the monitoring of the evolution of resistance of pneumococci to antibiotics in France. Between 1997 and 2007, 2427 strains of Streptococcus pneumoniae were isolated in part from cerebrospinal fluids, blood and middle ear fluid, from children and adults. The prevalence of pneumococci with a decreased susceptibility to penicillin (PDSP) decreased strongly in region Centre: 56.8 % in 2001, 39.6 % en 2007. These data are similar to the French national data over the same period.

[Prevalence of extended-spectrum beta-lactamases of the CTX-M type producing Escherichia coli and Klebsiella pneumoniae in Bretonneau hospitals (CHRU Tours)]. / Prévalence des souches de Escherichia coli et de Klebsiella pneumoniae productrices de beta-lactamases à spectre étendu de type CTX-M à l'hôpital Bretonneau (CHRU de Tours).

The CTX-M type extended spectrum beta-lactamases constitute a rapidly growing cluster of enzymes that have disseminated geographically. This study evaluates the prevalence of these enzymes in the university hospital in Tours, in 2007. Twenty-eight strains were studied: 21 Escherichia coli and seven Klebsiella pneumoniae. The gene bla(CTX-M) was detected by real-time PCR for 27 strains. The CTX-M-1 group, including CTX-M-15, was the most frequent CTX-M-type enzyme.

Appearance of aac(6')-Ib-cr gene among extended-spectrum beta-lactamase-producing Enterobacteriaceae in a French hospital.

OBJECTIVES: The aac(6')-Ib gene encodes many variants of an aminoglycoside-acetyltransferase enzyme that is responsible for amikacin resistance. Recently, a new variant aac(6')-Ib-cr capable of modifying aminoglycosides and fluoroquinolones has been described. The aim of our study was to observe the appearance and the location of the aac(6')-Ib gene in extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae strains. METHODS: Sixty-six and nine non-clonal ESBL-producing Enterobacteriaceae strains were isolated, respectively, for one 3-year period from 1999 to 2001 and one 2-month period in 2005 in a French Hospital (Paris, France). RESULTS: Among these isolates, 35 of them carried the aac(6')-Ib gene. Fourteen out of the aac(6')-Ib genes of the period 1 and two of the period 2 were genes cassette located within class 1 integrons, whereas 16 and 3, respectively, were outside integrons. One of these encoded an aminoglycoside-acetyltransferase enzyme leading to an acetyltransferase that confers resistance to all aminoglycosides. The new -cr variant of aac(6')-Ib was detected in three Escherichia coli isolates in 2005 always associated with CTX-M-15 enzyme. CONCLUSIONS: The aac(6')-Ib-cr gene, responsible for antibiotic resistance to two very different drugs, is emerging in ESBL-producing Enterobacteriaceae strains isolated in France especially in strains carrying the bla(CTx-M-15) gene.

Incidence of class A extended-spectrum beta-lactamases in Champagne-Ardenne (France): a 1 year prospective study.

OBJECTIVES: To assess the frequency and diversity of extended spectrum beta-lactamases (ESBLs) in the Champagne-Ardenne region France, and to identify genetic elements associated with the bla(CTX-M) genes. METHODS: During 2004, all the non-duplicate isolates of Pseudomonas aeruginosa and Acinetobacter baumannii resistant to ceftazidime and of Enterobacteriaceae intermediate or resistant to ceftazidime and/or cefotaxime, screening samples excluded, were collected in 10 public hospitals and 3 private clinics. bla genes were sequenced and bla(CTX-M) environment characterized by PCR mapping. RESULTS: In Enterobacteriaceae (138/21 861; 0.6%), ESBLs were predominantly TEM-24 (n = 52; 37.7%) and CTX-M-15 (n = 37; 26.8%). Three new enzymes were identified, CTX-M-61 (CTX-M-1 group), TEM- and SHV-type. A. baumannii (n = 5) produced VEB-1 and P. aeruginosa (n = 2) SHV-2a. ISEcp1 was detected in 22/27 strains, disrupted in 7 of them. The IS903-like element was downstream of bla(CTX-M-14) and bla(CTX-M-16). ISCR1 was found upstream of bla(CTX-M-2) and bla(CTX-M-9), and ISCR1 and bla(CTX-M-2) were located on a sul1-type class 1 integron. In comparison with 2001-02, ESBL distribution among Enterobacteriaceae showed an increase in CTX-M-type (44.9% vs 3.7% P < 10(-7)) due to Escherichia coli CTX-M-15 and to the almost total disappearance of TEM-3 (0.9% vs 51.2%). E. coli was the most frequent species (50.0% vs 5.1% in 1998) despite a similar prevalence to that in 1998 (0.5% vs 0.2%). CONCLUSIONS: A careful detection of bla(CTX-M)-type spread to other species would help to anticipate clonal endemics such as those observed in Enterobacter aerogenes TEM-24.

Spread of novel expanded-spectrum beta-lactamases in Enterobacteriaceae in a university hospital in the Paris area, France.

In 2002, 28 non-duplicate enterobacterial isolates producing extended-spectrum beta-lactamases (ESBLs) were collected from infected patients at the Bicêtre Hospital in Paris, France. Escherichia coli was the predominant ESBL-positive enterobacterial species, comprising ten (36%) of the isolates. CTX-M enzymes (CTX-M-3, CTX-M-10, CTX-M-14 and CTX-M-15) were produced by 11 (39%) of the isolates (six E. coli, two Enterobacter cloacae, one Enterobacter aerogenes, one Proteus mirabilis and one Citrobacter freundii). Other ESBLs, such as VEB-1 and PER-1, were also detected, but less frequently.

Uraemia is necessary for erythropoietin-induced hypertension in rats.

1. There is no experimental proof that renal insufficiency is a necessary condition for hypertension during erythropoietin treatment. 2. The present study compares the effect of 3 weeks treatment with r-hu EPO (50 i.u./kg) on systolic blood pressure (SBP), haematocrit and plasma cGMP in an animal model of chronic renal failure (remnant kidney model excision) and sham-operated rats. 3. Sub-total nephrectomy induced a significant fall in haematocrit and a significant increase in plasma creatinine levels. Treatment with r-hu EPO resulted in a significant haematocrit increase in uraemic as well as in non-uraemic rats. Despite this effect, r-hu EPO treatment had no effect on SBP in sham-operated rats. On the contrary, this treatment caused significant SBP elevation in uraemic rats; in these rats, SBP increase did not correlate with haematocrit increase. 4. Plasma cGMP concentrations were significantly higher in uraemic compared to sham-operated rats and were not modified by r-hu EPO treatment. 5. This study provides evidence that renal insufficiency in rats is a prerequisite for the development of hypertension during erythropoietin treatment.

Alterations in atrial natriuretic peptide gene expression during endurance training in rats.

Spontaneous and experimental rises of intracardiac pressure and/or volume increase the level of atrial natriuretic (ANP) mRNA in rat atrial tissue. There is expanding evidence that ANP synthesis is increased in the ventricle under such conditions. However, little is known with regard to the myocardial ANP synthesis response to physical training. In this study, plasma and atrial immunoreactive ANP concentrations were measured in Sprague-Dawley rats trained on a treadmill and compared to sedentary controls. Atrial natriuretic peptide mRNA was detected in the heart cavities of each group by dot-blot hybridization analysis. Physical training reduced the mean immunoreactive ANP plasma levels from 405 +/- 99 to 303 +/- 45 ng/l (p < 0.05). Immunoreactive ANP in the left atrium was depleted after endurance training, while immunoreactive ANP concentration in the right atrium was unaffected. Physical training resulted in a 70% (p < 0.01) rise in ANP mRNA of the right atrium, while no changes in the other compartments were found. These data indicate that during physical training: ANP mRNA does not increase in ventricles; despite depletion of immunoreactive ANP in the left atrium, no corresponding changes of ANP mRNA are detected; and ANP mRNA increases in the right atrium while its immunoreactive ANP does not. These findings suggest that during chronic exercise the ratio between immunoreactive ANP and ANP gene expression in the atria may be altered.

Incidence of bacteraemia or fever during transoesophageal echocardiography: a prospective study of 82 patients.

The incidence of bacteraemia during transoesophageal echocardiography (TEE) was evaluated in a prospective study of 82 consecutive patients. Three series of blood cultures were carried out for each patient: from group 1 (n = 44), prior to the examination, at the end of the examination and 15 min afterwards. For group 2 (n = 38), blood cultures were performed prior to the examination, 10 min after the start and immediately after the end. A single positive blood culture was detected in two patients. For the first patient, blood culture at the end of the examination demonstrated Corynebacteria, and for the second, Staphylococcus epidermidis was identified on cultures taken during the examination. During the first 24 h, a transient subfebrile temperature was recorded in 15% of the patients, including the patient with the Corynebacteria-positive blood culture. By mid-term (6 months) no patient had developed endocarditis. Our findings suggest that antibiotic prophylaxis during TEE is not warranted.

Angiotensin-converting enzyme inhibition does not suppress plasma angiotensin II increase during exercise in humans.

Physical effort stimulates the reninangiotensin system (RAS). We studied the effect of an angiotensin-converting enzyme inhibitor (ACE inhibitor) in a double-blind placebo-controlled study, on eight volunteers undergoing physical stress on an ergometric bicycle. The effects of captopril (C) (50 mg, three times daily for 3 days) on arterial pressure (AP), O2 consumption (VO2), variations in auricular natriuretic factor (ANF), renin, angiotensin II (AII) plasma levels, as well as glomerular filtration rate (GFR) and microalbuminuria (MA) were evaluated. The different parameters were compared by analysis of variance (ANOVA). The pressure profile and VO2 were not modified by ACE inhibitor. Exercise stimulates release of renin; this action was greater with captopril administration (treatment effect: p < 10(-4), indicating blockade of the RAS. This inhibition was incomplete because AII levels increased markedly when captopril was given (no treatment effect: p < 0.37). Finally, ACE inhibitor resulted in decreased GFR (p = 115 +/- 5.8 ml/mn-1, C = 91.1 +/- 4, p < 0.05) with exercise without modification of MA. ACE inhibitor administration does not modify the physical performance of nonathletic subjects; AII is significantly increased with exercise despite captopril treatment; ACE inhibitor decreases GFR significantly but does not influence MA with prolonged physical effort.

[An evaluation of the therapeutic trials aimed at regression of ventricular hypertrophy in arterial hypertension]. / Bilan des essais thérapeutiques visant à faire régresser l'hypertrophie ventriculaire gauche dans l'hypertension artérielle.

Left ventricular hypertrophy (LVH) which is a mechanism of adaptation of the heart to hypertension (HT) may become a cardiovascular risk factor independent of the HT which has caused it. Causing the regression of LVH is thus one of the mid-term aims of antihypertensive therapy. Certain antihypertensive drugs are capable of producing an early and durable regression of LVH: methyldopa, beta-blockers, ACEI, calcium blockers. The effect of mass reduction is moderate or doubtful with diuretics, while it is nil or inconstant with vasodilators. The regression of LVH in HT raises various problems: 1) reliability of the measurement technique, 2) inter-individual and inter-drug variations, 3) favourable nature of regression, 4) preventive effect of regression against cardiovascular complications. Finally, in the light of recent studies it appears that early treatment of HT may prevent the onset of LVH.

[Antihypertensive treatment and remission of left ventricular hypertrophy. Critical study]. / Traitement antihypertenseur et régression de l'hypertrophie ventriculaire gauche. Etude critique.

Left ventricular hypertrophy which is the adaptive mechanism of the heart to hypertension may become a cardiovascular risk factor independent of the hypertension which induced it: the regression of left ventricular hypertrophy therefore constitutes one of the medium-term objectives of antihypertensive therapy. Some antihypertensive drugs make the left ventricular hypertrophy regress early and permanently: methyldopa, betablockers, converting enzyme inhibitors, calcium antagonists. The reduction of myocardial mass is slight or debatable with diuretics and absent or inconstant with vasodilator therapy. The regression of left ventricular hypertrophy in hypertension raises several problems: the reliability of methods of measurement; inter-individual and inter-drug variations; the beneficial nature of this regression; the preventive effect of regression of left ventricular hypertrophy on cardiovascular complications. In the light of recent trials, early treatment of hypertension may prevent the development of left ventricular hypertrophy.

[Atrial natriuretic peptide response to physical exercise is inhibited by an antagonist of the opioid receptors]. / La réponse du peptide natriurétique auriculaire à l'exercise physique, est inhibée par un antagoniste des récepteurs opiacés.

It was been shown that physical exercise increases plasma atrial natriuretic peptide (ANP) level. This effect was attributed to the hemodynamic changes of exercise which could increase atrial volume and result in ANP secretion. On the other hand, it was evidenced that morphine and opiate peptides greatly stimulate ANP release. To evaluate to what extent the endogenous opioid secretion during exercise induces the ANP release, six healthy volunteers male trained subjects were submitted to two maximal exercise tests with and without (placebo) opiate receptors blockade by naltrexone (50 mg per os). Blood samples were drawn before (rest) and after maximal exercise in order to measure by radioimmunological methods human atrial natriuretic peptide (alpha-h-ANP), beta-endorphin, plasma aldosterone (ALD), plasma renin activity (PRA) and corticotrophin (ACTH). Expired gas was collected during exercise to measure oxygen consumption. Subjects reached the same value of maximal oxygen consumption (VO2 max) at the end of exercise whatever treatment. Plasma ANP level at rest decreases slightly after administration of naltrexone (32.8 +/- 6.3 pg/ml with placebo versus 21.3 +/- 4.6 pg/ml with naltrexone) but the response to physical exercise was significantly reduced by naltrexone (73.3 +/- 14.9 pg/ml with placebo versus 46.9 +/- 8.6 pg/ml with naltrexone) (p less than 0.05). There was no statistical difference according to the treatment between the plasma levels of beta-endorphin, PRA and ACTH at rest as well as at the end of a maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)