Antistaphylococcal penicillins vs. cefazolin in the treatment of methicillin-susceptible Staphylococcus aureus infective endocarditis: a quasi-experimental monocentre study.

Whether cefazolin is as effective and safer than antistaphylococcal penicillins (ASPs) for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) is still debated in the absence of a randomized controlled trial. In this quasi-experimental study, we aimed to assess the effectiveness and safety of these two treatments in MSSA-IE, using the ASPs nationwide shortage in April 2016 as a unique opportunity to overcome the indication bias associated with observational studies. In this single-centre study, we compared patients with Duke-Li definite MSSA-IE treated with ASPs from January 2015 to March 2016 versus those treated with cefazolin from April 2016 to December 2018, when ASPs were not available. Effectiveness outcome was 90-day all-cause mortality. Safety outcomes included significant decrease in GFR and significant increase in serum liver enzymes. Logrank test was used to compare survival rates. Of 73 patients with MSSA-IE, 35 and 38 were treated with ASPs and cefazolin, respectively. Baseline patients' characteristics (demography, native or prosthetic valve IE, clinical characteristics, cardiac and septic complications) were similar between groups. Ninety-day all-cause mortality was 28.6% and 21.1%, in patients treated with ASPs and cefazolin, respectively (logrank p = 0.5727). There was no difference between groups for incident renal or liver toxicity events: acute kidney injury 45.7% vs. 44.7% (p = 0.933), increased ALT 5.7% vs. 13.2% (p = 0.432), bilirubin increase 5.7% vs. 10.5% (p = 0.676), in ASPs vs. cefazolin groups, respectively. In this quasi-experimental, effectiveness and safety did not statistically differ between ASPs and cefazolin for MSSA-IE treatment.

N-oleoyldopamine modulates activity of midbrain dopaminergic neurons through multiple mechanisms.

N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in catecholaminergic neurons. The present study investigates OLDA targets in midbrain dopaminergic (DA) neurons. Substantia Nigra compacta (SNc) DA neurons recorded in brain slices were excited by OLDA in wild type mice. In transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, however, SNc DA neurons displayed sustained inhibition of firing. In the presence of the dopamine type 2 receptor (D2R) antagonist sulpiride or the dopamine transporter blocker nomifensine no such inhibition was observed. Under sulpiride OLDA slightly excited SNc DA neurons, an action abolished upon combined application of the cannabinoid1 and 2 receptor antagonists AM251 and AM630. In ventral tegmental area (VTA) DA neurons from TRPV1 KO mice a transient inhibition of firing by OLDA was observed. Thus OLDA modulates the firing of nigrostriatal DA neurons through interactions with TRPV1, cannabinoid receptors and dopamine uptake. These findings suggest further development of OLDA-like tandem molecules for the treatment of movement disorders including Parkinson's disease.

Inventory of Extended-Spectrum-ß-Lactamase-Producing Enterobacteriaceae in France as Assessed by a Multicenter Study.

The objective of this study was to perform an inventory of the extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae isolates responsible for infections in French hospitals and to assess the mechanisms associated with ESBL diffusion. A total of 200 nonredundant ESBL-producing Enterobacteriaceae strains isolated from clinical samples were collected during a multicenter study performed in 18 representative French hospitals. Antibiotic resistance genes were identified by PCR and sequencing experiments. The clonal relatedness between isolates was investigated by the use of the DiversiLab system. ESBL-encoding plasmids were compared by PCR-based replicon typing and plasmid multilocus sequence typing. CTX-M-15, CTX-M-1, CTX-M-14, and SHV-12 were the most prevalent ESBLs (8% to 46.5%). The three CTX-M-type EBSLs were significantly observed in Escherichia coli (37.1%, 24.2%, and 21.8%, respectively), and CTX-M-15 was the predominant ESBL in Klebsiella pneumoniae (81.1%). SHV-12 was associated with ESBL-encoding Enterobacter cloacae strains (37.9%). qnrB, aac(6')-Ib-cr, and aac(3)-II genes were the main plasmid-mediated resistance genes, with prevalences ranging between 19.5% and 45% according to the ESBL results. Molecular typing did not identify wide clonal diffusion. Plasmid analysis suggested the diffusion of low numbers of ESBL-encoding plasmids, especially in K. pneumoniae and E. cloacae However, the ESBL-encoding genes were observed in different plasmid replicons according to the bacterial species. The prevalences of ESBL subtypes differ according to the Enterobacteriaceae species. Plasmid spread is a key determinant of this epidemiology, and the link observed between the ESBL-encoding plasmids and the bacterial host explains the differences observed in the Enterobacteriaceae species.

Molecular epidemiology of OXA-48-producing Klebsiella pneumoniae in France.

We characterized 53 OXA-48-producing Klebsiella pneumoniae (OXA-48-Kp) isolated between 2011 and 2013 in 21 French hospitals. All the isolates were genotyped using MLST and PFGE and the population structure of the species was determined by a nucleotide-based analysis of the entire K. pneumoniae MLST database. Most of the OXA-48-Kp isolates also produced CTX-M-15 and remained susceptible to imipenem and meropenem. The isolates were distributed into 20 STs, of which five were dominant (ST15, ST101, ST147, ST395 and ST405). All the OXA-48-Kp clustered in the major clade of K. pneumoniae KpI.

Antibiolor, the Lorraine antibiology network: update on 7 years of activity.

OBJECTIVE: The objective of the study was to assess the activity of the Antibiolor network, created in 2003, to promote antibiotic stewardship in Lorraine, and comply with the French Ministry guidelines issued in May 2002. METHODS: The authors described the objectives and structure of the network, actions implemented with physicians, pharmacists, community or hospital biologists, and evaluation. RESULTS: The network is made up of five committees supervised by a pilot committee. Over the previous 7 years, various actions were undertaken such as the drafting of guidelines for the hospitals and general practitioners, the creation of a hotline for advice on antibiotic treatment, the creation of a website, and giving information on infectious diseases via a quarterly letter sent to healthcare professionals. The network participated in continuous medical education for practitioners and organized the evaluation of professional practice in Lorraine hospitals. It also helped set up a network of community private laboratories for the study of resistance in the most frequently isolated bacteria, and implemented the monitoring of antibiotic consumption in hospitals. CONCLUSION: After 7 years, the Lorraine antibiology network has proved its beneficial role in terms of communication and scientific information for antibiotic stewardship. The Antibiolor network would like to follow other indicators in the future, such as the evolution of community antibiotic consumption in partnership with the public healthcare insurance.

How to improve the collection and analysis of hospital antibiotic consumption: preliminary results of the ConsoRes software experimental implementation.

OBJECTIVE: The online software ConsoRes is used to collect and analyze data on antibiotic consumption and evolution of bacterial resistance in healthcare institutions in every hospital ward (HW). We report the first results of ConsoRes implementation in the northeast hospitals of France. METHODOLOGY: ConsoRes was implemented in January 2011, in nine volunteer hospitals after performing an onsite assessment. Five of these hospitals were already monitoring antibiotic consumption with a network such as Raisin ATB or Antibiolor, providing feedback on the various evaluation tools. RESULTS: The ConsoRes data collection import function meets expectations of pharmacists, bacteriologists, or clinicians since it is user friendly, prevents redundant data input, and allows data transfer to the national databases. Importing the hospital organizational structure prevents mistakes on consumption allocation, which was noted in the previous databases, and makes comparison and benchmark analysis reliable. ConsoRes also provides a rapid consumption data feedback to all registered users within the hospital, whether in charge of a ward (clinician) or having a transversal function (pharmacist, bacteriologist). The availability of an automatic standard report or of an online customized report is another major feature of ConsoRes. CONCLUSION: Besides providing surveillance, the concomitant analysis of local antibiotic consumption and bacterial resistance should have an educational impact by allowing each user to implement actions within the framework of antibiotic stewardship.

[Staphylococcus aureus bacteremia and endocarditis]. / Bactériémies et endocardites àStaphylococcus aureus.

The prevalence of Stapylococcus bacteriaemia is increasing worldwide, because of the increasing use of invasive procedures leading to nosocomial infections, but also of a changing way of life (increasing fashion for tattoos or piercing, use of intravenous drugs). Infective endocarditis develops in 10-30% of the cases of staphylococcus bacteriaemia. Staphylococcus aureus endocarditis must be suspected when it develops in the year following heart surgery or implantation of permanent devices. In drug users, it usually involves the tricuspid valve. According to the resistance of the germ to meticillin, antibiotic therapy uses a combination of intravenous penicillin or glycopeptide and an aminoside. Other antibiotics such as fosfomycin, rifampicin, fusidic acid, or clindamycin can be used when aminosides are contra-indicated. The role of newer antibiotic agents, such as daptomycin or linezolide, remains to be established.

Campylobacter fetus meningitis in a diabetic adult cured by imipenem.

Reported here is the successful management of a severe case of Campylobacter fetus subspecies fetus meningitis, complicated by septic shock, in a patient without overt immunosuppression who was cured by imipenem. Meningitis caused by C. fetus has rarely been reported in adults, and only exceptionally in non-immunocompromised patients, and septic shock has not previously been reported as a complication of such meningitis. The best antibiotic regimen for treating this condition remains to be determined. Imipenem has displayed high in vitro activity against C. fetus but has been used rarely in clinical practice. It was administered in this case with good results.

[Accuracy of four agar diffusion methods and the Vitek 2 automated system for the detection of the methicillin resistance in coagulase negative staphylococci]. / Performance de quatre méthodes d' antibiogramme par diffusion en milieu gélosé et de la l'automate Vitek 2 pour la détection de la méticillino-resistance chez les staphylocoques à coagulase négative.

AIM OF THE STUDY: Technical difficulties may occur in the detection of methicillin resistance in coagulase negative staphylococci. Phenotypic methods, such as disk diffusion testing, sometimes fail to detect methicillin resistance because of its poor expression. Four of these methods were compared with the VITEK 2 system. MATERIALS AND METHODS: The accuracy of the VITEK 2 system and the agar diffusion methods according to the current CASFM and NCCLS guidelines were assessed for methicillin susceptibility testing of 70 coagulase negative staphylococci isolates harboring the mecA gene for which the detection of the methicillin resistance was particularly difficult: the CASFM recommendations applied in 1998 failed to categorize them as methicillin-resistant. RESULTS: Among the different methods currently suggested by the CASFM, those using a heavy inoculum and a hypersaline medium give better results, but they remain however less efficient than the NCCLS recommendations testing (sensitivity: 71-86% vs. 94-94% respectively). The VITEK 2 was more efficient (sensitivity: 91%) than the disk diffusion methods recommended by the CASFM and slightly less efficient than the method recommended by the NCCLS. CONCLUSION: The VITEK 2 automated system, compared with the disk diffusion methods, showed adequate accuracy for detection of oxacillin resistance in coagulase negative staphylococci.

[Comparison of the in vitro sensitivity to cidofovir and ganciclovir of clinical cytomegalovirus isolates. Coordinated Action Group 11]. / Comparaison de la sensibilité in vitro au cidofovir et au ganciclovir des isolats cliniques de cytomégalovirus. Groupe de l'Action Coordonnée 11.

Cidofovir (CDF) or Vistid is a monophosphate nucleoside analogue that inhibits the DNA polymerase of herpes viruses including the cytomegalovirus (CMV). CDF is active on GCV-resistant strains with a mutation on the phosphotransferase gene (UL97). However, DNA polymerase gene mutations that induce resistance to GCV are responsible for cross-resistance to CDF. Resistance phenotypes to GCV and CDF were determined for 57 CMV strains isolated from blood and urine samples. Sixteen strains were recovered after CDF therapy. Of the remaining 41 CDF-naive strains, 34 were susceptible and seven resistant to GCV. Fifty percent inhibitory concentrations (IC50) for CDF were in the 0.2-2.6 microM range for CDF-naive strains susceptible to GCV. For GCV-resistant strains, IC50 values for CDF were < or = 3 microM for strains with a low level of resistance to GCV (GCV IC50 < 30 microM) and > or = 6 microM for three of the five strains with a high level of resistance to GCV (GCV IC50 > or = 30 microM).

[Renal artery stenosis and aorto-iliac restoration: is it necessary to do extensive evaluation?]. / Sténoses des artères rénales et restauration aorto-iliaque: faut-il faire un bilan extensif?

In patients with aortoiliac disease and a stenosis of one or two renal artery, renal hypertension is rarely the sole mechanism of the elevated blood pressure. The preservation of nephron mass being the aim of the renal revascularization, we firmly believe that only three tests are required for the operative decision: renal ultrasonography, nephroscintigraphy and global and selective aortography.

[Septicemia caused by A, B, C and G groups of beta-hemolytic streptococci]. / Septicémies à streptocoques bêta-hémolytiques des groupes A, B, C et G.

During a five and a half years' period, 805 strains of beta-haemolytic groups A, B, C and G streptococci were isolated. Among these, 28 were responsible for bacteremia; 57 percent group B and 32 percent group A. All strains were susceptible to beta-lactam antibiotics; 4 strains were resistant to macrolides. The majority of patients had underlying diseases. Mortality was high in this group.

Late results of reconstructive surgery for renovascular hypertension.

In order to evaluate the late results of reconstructive surgery for renovascular hypertension, a review was made on a series of 120 consecutive patients who underwent operations over a 11 year period. There were 82 males (68.3%) and 38 females (31.7%) with a mean age of 48.4 years. Renal artery by-pass grafts were used in 90% (120/133), a thromboendarterectomy in 5.2% (7/133), and other surgical procedures were performed in 4.8% (6/133). Associated vascular procedures were performed in 38.3% (46/120) of patients. Operative mortality was 2.5% (3/120) overall; there was no mortality in the isolated renal artery reconstructions. There was a clinical success (after a mean follow-up of 48 months) in 80.4% of patients. The most important factors influencing clinical result after renal revascularization were: a generalized atherosclerosis (p less than 0.05), duration of hypertension (p less than 0.01) and the early post-operative response of the blood pressure (p less than 0.01). The overall five- and ten-year actuarial survival probabilities were 85 and 68%, respectively. The most common causes of death were myocardial infarction, stroke and cancer. Cox regression analysis for variables influencing survival indicated that persistence of severe hypertension was the major determinant of late survival (p less than 0.05). Hypertension in females is better tolerated, while younger patients appear to have better results and late survival after surgical treatment.