Xenopus GLP-1-based glycopeptides as dual glucagon-like peptide 1 receptor/glucagon receptor agonists with improved in vivo stability for treating diabetes and obesity.

Peptide dual agonists toward both glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) are emerging as novel therapeutics for the treatment of type 2 diabetes mellitus (T2DM) patients with obesity. Our previous work identified a Xenopus GLP-1-based dual GLP-1R/GCGR agonist termed xGLP/GCG-13, which showed decent hypoglycemic and body weight lowering activity. However, the clinical utility of xGLP/GCG-13 is limited due to its short in vivo half-life. Inspired by the fact that O-GlcNAcylation of intracellular proteins leads to increased stability of secreted proteins, we rationally designed a panel of O-GlcNAcylated xGLP/GCG-13 analogs as potential long-acting GLP-1R/ GCGR dual agonists. One of the synthesized glycopeptides 1f was found to be equipotent to xGLP/GCG-13 in cell-based receptor activation assays. As expected, O-GlcNAcylation effectively improved the stability of xGLP/GCG-13 in vivo. Importantly, chronic administration of 1f potently induced body weight loss and hypoglycemic effects, improved glucose tolerance, and normalized lipid metabolism and adiposity in both db/db and diet induced obesity (DIO) mice models. These results supported the hypothesis that glycosylation is a useful strategy for improving the in vivo stability of GLP-1-based peptides and promoted the development of dual GLP-1R/GCGR agonists as antidiabetic/antiobesity drugs.

Postexposure Prophylaxis and Treatment of Bacillus anthracis Infections: A Systematic Review and Meta-analyses of Animal Models, 1947-2019.

BACKGROUND: Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies. METHODS: We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans. RESULTS: We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, ß-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx. CONCLUSIONS: These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.

Long-Term Impact of Suppressive Antibiotic Therapy on Intestinal Microbiota.

The aim was to describe the safety of indefinite administration of antibiotics, the so-called suppressive antibiotic therapy (SAT) and to provide insight into their impact on gut microbiota. 17 patients with SAT were recruited, providing a fecal sample. Bacterial composition was determined by 16S rDNA massive sequencing, and their viability was explored by PCR-DGGE with and without propidium monoazide. Presence of antibiotic multirresistant bacteria was explored through the culture of feces in selective media. High intra-individual variability in the genera distribution regardless of the antibiotic or antibiotic administration ingestion period, with few statistically significant differences detected by Bray-Curtis distance-based principle component analysis, permutational multivariate analysis of variance and linear discriminant analysis effect size analysis. However, the microbiota composition of patients treated with both beta-lactams and sulfonamides clustered by a heat map. Curiously, the detection of antibiotic resistant bacteria was almost anecdotic and CTX-M-15-producing E. coli were detected in two subjects. Our work demonstrates the overall clinical safety of SAT and the low rate of the selection of multidrug-resistant bacteria triggered by this therapy. We also describe the composition of intestinal microbiota under the indefinite use of antibiotics for the first time.

Characterization of SCCmec, spa types and Multi Drug Resistant of methicillin-resistant Staphylococcus aureus isolates among inpatients and outpatients in a referral hospital in Shiraz, Iran.

OBJECTIVES: Molecular typing such as spa typing is used to control and prevent Staphylococcus aureus widespread in hospitals and communities. Hence, the aim of this study was to find the most common types of S. aureus strain circulating in Shiraz via spa and SCCmec typing methods. RESULTS: Total of 159 S. aureus isolates were collected from two tertiary hospitals in Shiraz. Isolates were identified by biochemical tests. Antimicrobial susceptibility tests were performed by standard disk diffusion method and then genetic analysis of bacteria was performed using SCCmec and spa typing. In this study 31.4% of the isolates were methicillin-resistant S. aureus. The majority of isolates were SSCmec type III. Spa type t030 was the most prominent type among MRSA strains. For the first time in Iran, spa003, t386, t1877, t314, t186, t1816, t304, t325, t345 were reported in this study. It was shown that there is a possibility that these spa types are native to this region. Our findings showed that SCCmec II, III and IV disseminate from hospital to community and vice versa. Thus, effective monitoring of MRSA in hospital and community is necessary.

Successful Treatment of Methicillin Susceptible Staphylococcus aureus Osteomyelitis with Oritavancin.

Staphylococcus aureus remains the most common causative pathogen in osteomyelitis. New or alternative therapies are often needed to treat S. aureus infections adequately in patients with drug allergies, treatment failures, or drug interactions. Oritavancin is a novel long-acting lipoglycopeptide approved by the U.S. Food and Drug Administration in 2014 for the treatment of acute bacterial skin and skin structure infections. With a terminal half-life of 8-10 days, oritavancin dosing regimens with infrequent parenteral administration now exist to treat infectious diseases such as osteomyelitis that would otherwise require daily dosing of intravenous antimicrobials for weeks; however, clinical experience is lacking. In this article, the first case of S. aureus osteomyelitis resulting from traumatic injury, successfully treated with oritavancin, is presented. Removal of the nail used for a comminuted tibial shaft fracture repair followed by a 6-week treatment course with oritavancin resulted in clinical response.

In vitro activity of Oritavancin against gram-positive pathogens isolated in Canadian hospital laboratories from 2011 to 2015.

Gram-positive bacterial pathogens isolated from patient specimens submitted to 15 Canadian hospital laboratories from 2011 to 2015 were tested in the coordinating laboratory for susceptibility to oritavancin and comparative antimicrobial agents using the Clinical and Laboratory Standards Institute M07-A10 (2015) broth microdilution method. Oritavancin's in vitro activity was equivalent to, or more potent than, vancomycin, daptomycin, linezolid, and tigecycline against methicillin-susceptible Staphylococcus aureus (n=2680; oritavancin MIC90, 0.12µg/mL; 99.9% oritavancin-susceptible), methicillin-resistant S. aureus (n=728; oritavancin MIC90, 0.12µg/mL; 99.7% oritavancin-susceptible), Streptococcus pyogenes (n=218; oritavancin MIC90, 0.25µg/mL; 100% oritavancin-susceptible), Streptococcus agalactiae (n=269; oritavancin MIC90, 0.12µg/mL; 100% oritavancin-susceptible), and vancomycin-susceptible Enterococcus faecalis (n=508; oritavancin MIC90, 0.06µg/mL; 100% oritavancin-susceptible). Oritavancin, dalbavancin, and telavancin demonstrated equivalent in vitro activities (MIC90, µg/mL) against 602 isolates of MSSA (0.06, 0.06, 0.06, respectively) and 144 isolates of MRSA (0.12, 0.06, 0.06, respectively) collected in 2015.

Potenciales indicaciones de dalbavancina en la práctica clínica / Potential indications of dalbavancin in clinical practice

Dalbavancina es un lipoglucopéptido semisintético con 2 propiedades distintivas del resto de miembros de su familia de antibióticos, que derivan de su estructura molecular: una actividad intrínseca mayor y una vida media muy prolongada que posibilita una posología semanal o bisemanal con dosis únicas de 1.000 o 1.500 mg, respectivamente. Esta semivida de eliminación hace a dalbavancina un antibiótico singular y permite diseñar nuevas estrategias de tratamiento que facilitan altas hospitalarias precoces sin necesidad de accesos vasculares y con garantía de cumplimiento terapéutico. Este fármaco podría ser aprovechado para resolver algunos de los problemas de manejo de la infección que se plantean con frecuencia en la práctica clínica diaria, particularmente en la consolidación del tratamiento de procesos agudos, en infecciones que precisan tratamiento prolongado y en la profilaxis de algunos cuadros clínicos recurrentes por cocos Gram positivos (AU)

Dalbavancin is a semisynthetic lipoglycopeptide with two properties that distinguish it from other members of the antibiotic family from which it is derived: a greater intrinsic activity and a very prolonged mean half-life that allows weekly or twice-weekly dosing with a single 1000 mg or 1500 mg dose, respectively. Because of this half-life, dalbavancin is a unique antibiotic. This drug allows the design of new treatment strategies that facilitate early hospital discharge without the need for vascular access and with guaranteed treatment adherence. Dalbavancin could be used to resolve some of the problems that commonly occur in the management of infections in daily clinical practice, particularly in consolidation therapy in acute processes, infections requiring prolonged treatment and in the prophylaxis of some recurrent processes caused by Gram-positive cocci (AU)

Weight gain by gut microbiota manipulation in productive animals.

Antibiotics, prebiotics and probiotics are widely used as growth promoters in agriculture. In the 1940s, use of Streptomyces aureofaciens probiotics resulted in weight gain in animals, which led to the discovery of chlortetracycline. Tetracyclines, macrolides, avoparcin and penicillins have been commonly used in livestock agriculture to promote growth through increased food intake, weight gain, and improved herd health. Prebiotic supplements including oligosaccharides, fructooligosaccharides, and galactosyl-lactose improve the growth performance of animals. Probiotics used in animal feed are mainly bacterial strains of Gram-positive bacteria and have been effectively used for weight gain in chickens, pigs, ruminants and in aquaculture. Antibiotics, prebiotics and probiotics all modify the gut microbiota and the effect of a probiotic species on the digestive flora is probably determined by bacteriocin production. Regulations governing the introduction of novel probiotics and prebiotics vary by geographical region and bias is very common in industry-funded studies. Probiotic and prebiotic foods have been consumed for centuries, either as natural components of food, or as fermented foods and it is possible to cause the same weight gain effects in humans as in animals. This review presents the use of growth promoters in food-producing animals to influence food intake and weight gain.

Casein glycomacropeptide for active distal ulcerative colitis: a randomized pilot study.

BACKGROUND: In ulcerative colitis (UC), dietary supplements may have anti-inflammatory properties and improve disease course. We investigated the effects of casein glycomacropeptide (CGMP), a fraction of bovine whey protein, in active UC. MATERIALS AND METHODS: In a randomized open-label intervention study, 24 patients with active UC involving 10-40 cm of the distal colon were randomized in a 2 : 1 ratio into two groups. The first group was administered their usual treatment plus a daily supplement of CGMP 30 g, and the second group was administered a dose escalation to 4800 mg oral mesalamine daily (standard treatment) for 4 weeks. Clinical, endoscopic, mucosal and circulating disease activity markers were monitored. Acceptance of and adherence to CGMP up to 8 weeks were documented. RESULTS: After 4 weeks of treatment, 10 of 16 (63%) patients who received CGMP had an unchanged or decreased Simple Clinical Colitis Activity Index (SCCAI), which was similar to the four of eight (50%) (P = 0·67) patients on the standard treatment. The number of patients in which SCCAI decreased by three or more did not differ between the two groups: nine of 16 (56%) in the CGMP group vs. four of eight (50%) in the standard treatment group (P = 0·77). Changes in disease extent and severity were similar between the two groups. CGMP was well tolerated and accepted by the patients. CONCLUSIONS: The addition of CGMP as a nutritional therapy to standard treatment was safe and accepted by patients with active distal UC. The disease-modifying effect of CGMP was similar to that of the mesalamine dose escalation.

Oritavancin: A Novel Lipoglycopeptide.

OBJECTIVE: To review the pharmacology, pharmacokinetics, drug interactions, microbiologic profile, dosage and administration, safety, clinical efficacy, and potential place in therapy for the new lipoglycopetide, oritavancin. DATA SOURCES: MEDLINE and PubMed searches of available literature in English were conducted for oritavancin. Principal supplementary sources include the Food and Drug Administration (FDA) package insert, and FDA/European Medicines Agency guidances on acute bacterial skin and skin structure infections (ABSSSI). STUDY SELECTION AND DATA EXTRACTION: Information from all stages of clinical development was evaluated to provide an overview of oritavancin, from in vitro susceptibility, to early human studies, to the latter stages of clinical trials. DATA SYNTHESIS: Oritavancin is a lipoglycopeptide antibiotic that has a mechanism of action and broad-spectrum gram-positive coverage similar to other glycopeptides. Compared with other glycopeptides, oritavancin minimum inhibitory concentrations tend to be lower. Oritavancin also has coverage against glycopeptide-resistant gram-positive organisms. Oritavancin does not require dose adjustment for mild-to-moderate hepatic or renal impairment, and its prolonged half-life of 245 hours allows for a one-time administration in the treatment of ABSSSI. In phase 2 and 3 clinical trials, oritavancin was shown to be well-tolerated in addition to being noninferior to vancomycin for the treatment of ABSSSI. The most common side effects experienced were gastrointestinal in nature. CONCLUSIONS: Oritavancin was approved by FDA for the treatment of ABSSSI in August 2014 and is marketed under the trade name Orbactiv. Its reduced dosing and monitoring requirements and efficacy against resistant gram-positive pathogens provide a unique profile that distinguishes it from current options in the treatment of ABSSSI.

Dalbavancin and Oritavancin: An Innovative Approach to the Treatment of Gram-Positive Infections.

Health care-associated infections, especially those caused by multidrug-resistant gram-positive organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), are a growing public health threat. In 2014, the U.S. Food and Drug Administration approved two new lipoglycopeptides, oritavancin and dalbavancin, for the treatment of acute bacterial skin and skin structure infections. The rationale for the development of these antimicrobials was partly to aid in the battle against vancomycin resistance in both Staphylococcus and Enterococcus. Considered a subclass of the glycopeptide antibiotics, the new lipoglycopeptides have similar mechanisms of action of binding to the carboxyl terminal d-alanyl-d-alanine residue of the growing peptide chains but differ from their parent glycopeptides by the addition of lipophilic tails. This addition allows for these agents to have prolonged half-lives, giving them unique dosing profiles. In addition, by concentrating at the site of action, they have increased potency against MRSA compared with vancomycin, the current mainstay of therapy. In this review, we focus on comparing and contrasting these two new agents with regard to their pharmacology, mechanisms of action, spectrum of activity, safety profiles, dosage and administration, and drug and laboratory interactions, and we review the clinical trials evaluating their use.

Oritavancin: a review in acute bacterial skin and skin structure infections.

Oritavancin (Orbactiv(®)) is a new generation lipoglycopeptide approved for use in adult patients with acute bacterial skin and skin structure infections (ABSSSI). It is administered as a single 1200 mg intravenous infusion over 3 h. In phase 3 trials in adult patients with ABSSSI, oritavancin was noninferior to vancomycin in terms of a composite outcome (cessation of spreading or reduction in the size of the baseline lesion, absence of fever and no rescue antibacterials required; primary endpoint) assessed at an US FDA-recommended early timepoint of 48-72 h after initiation of treatment. Oritavancin was also noninferior to vancomycin in terms of a ≥20 % reduction in the baseline lesion size at the early timepoint and clinical cure rate 7-14 days after the end of treatment. Oritavancin was generally well tolerated in the phase 3 trials, with most treatment-emergent adverse reactions being mild in severity. The most common adverse events occurring in oritavancin recipients were nausea, headache, vomiting, limb and subcutaneous abscesses, and diarrhoea. Oritavancin offers a number of potential advantages, including a convenient single dose treatment that may shorten or eliminate hospital stays, a reduction in healthcare resource utilization and cost, no need for dosage adjustment in patients with mild to moderate hepatic or renal impairment, no need for therapeutic drug monitoring, and elimination of compliance concerns. Therefore, oritavancin is a useful treatment option for adults with ABSSSI.

[Cloxacillin-susceptible Staphylococcus aureus with high MIC to glycopeptides. Ever we use cloxacillin?]. / Staphylococcus aureus sensible a cloxacilina con CMI elevada a glucopéptidos. ¿Ponemos siempre cloxacilina?

Staphylococcus aureus infections are yet an important cause of morbidity and mortality despite of numerous effective anti-staphylococcal antibiotics available. There has been an increasing incidence of methicillin-resistant strains which might have led to a wider use of vancomycin. This seems to ride alongside a covert progressive increase of S. aureus vancomycin minimum inhibitory concentration. In this way, the emergence of vancomycin-intermediate S. aureus (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant S. aureus. Ultimately, various debate issues have arisen regarding the emergence of S. aureus strains with decreased vancomycin susceptibility, within the range still considered sensitive. These strains have shown a different clinical behaviour regardless of vancomycin use, both in methicillin resistant and sensitive S. aureus. The emergence of increasing vancomycin-resistance in S. aureus isolates, has stirred up the basis of therapeutic approach in staphylococcal infections. There is yet much to explore to better define the impact of higher vancomycin minimum inhibitory concentration in staphylococcal infections.

Impact of Molecular Epidemiology and Reduced Susceptibility to Glycopeptides and Daptomycin on Outcomes of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was associated with high mortality, but the risk factors associated with mortality remain controversial. METHODS: A retrospective cohort study was designed. All patients with MRSA bacteremia admitted were screened and collected for their clinical presentations and laboratory characteristics. Minimum inhibitory concentration (MIC) and staphylococcal cassette chromosome mec (SCCmec) type of bacterial isolates were determined. Risk factors for mortality were analyzed. RESULTS: Most MRSA isolates from the 189 enrolled patients showed reduced susceptibility to antibiotics, including MIC of vancomycin ≥ 1.5 mg/L (79.9%), teicoplanin ≥ 2 mg/L (86.2%), daptomycin ≥ 0.38 mg/L (73.0%) and linezolid ≥ 1.5 mg/L (64.0%). MRSA with vancomycin MIC ≥ 1.5 mg/L and inappropriate initial therapy were the two most important risk factors for mortality (both P < 0.05; odds ratio = 7.88 and 6.78). Hospital-associated MRSA (HA-MRSA), carrying SCCmec type I, II, or III, was associated with reduced susceptibility to vancomycin, teicoplanin or daptomycin and also with higher attributable mortality (all P < 0.05). Creeping vancomycin MIC was linked to higher MIC of teicoplanin and daptomycin (both P < 0.001), but not linezolid (P = 0.759). CONCLUSIONS: Giving empirical broad-spectrum antibiotics for at least 5 days to treat catheter-related infections, pneumonia, soft tissue infection and other infections was the most important risk factor for acquiring subsequent HA-MRSA infection. Choice of effective anti-MRSA agents for treating MRSA bacteremia should be based on MIC of vancomycin, teicoplanin and daptomycin. Initiation of an effective anti-MRSA agent without elevated MIC in 2 days is crucial for reducing mortality.

Use of ceftaroline after glycopeptide failure to eradicate meticillin-resistant Staphylococcus aureus bacteraemia with elevated vancomycin minimum inhibitory concentrations.

Elevated minimum inhibitory concentrations (MICs) of vancomycin against meticillin-resistant Staphylococcus aureus (MRSA) and the emergence of heteroresistant S. aureus strains have led to increased use of anti-MRSA antibiotics other than vancomycin. Ceftaroline fosamil is a novel cephalosporin with activity against MRSA, but there are limited clinical data on its use for MRSA bacteraemia (MRSAB) and against strains exhibiting high vancomycin MICs (2-4 µg/mL). This multicentre, retrospective, case-control study compared the microbiological and clinical effectiveness of ceftaroline used after vancomycin failure with that of vancomycin-treated controls for the treatment of MRSA with vancomycin MICs ≥ 2 µg/mL. In total, 32 patients were matched 1:1 with respect to vancomycin MIC, age and origin of bacteraemia. In the ceftaroline group, patients received prior MRSA therapy for a median of 5 days [interquartile range (IQR), 3-15.8 days] prior to switching to ceftaroline. Median time to eradication of MRSA was significantly less after treatment with ceftaroline compared with vancomycin [4 days (IQR, 3-7.5 days) vs. 8 days (IQR, 5.8-19.5 days); P=0.02]. Both clinical success at the end of treatment and recurrence of MRSA at Day 7 were trending towards being inferior in the vancomycin group, although the results did not attain statistical significance [81% vs. 44% (P=0.06) and 6% vs. 38% (P=0.08), respectively]. Ceftaroline added at the point of vancomycin failure resolves MRSAB more rapidly and with a higher rate of clinical success, therefore ceftaroline should be considered as an alternative for these difficult-to-treat infections.

Oritavancin: first global approval.

Oritavancin (Orbactiv(®)) is a lipoglycopeptide antibacterial drug with activity against Gram-positive bacteria developed by The Medicines Company as a single-dose treatment for acute bacterial skin and skin structure infections (ABSSSI). The drug received its first global approval for this indication in the US in August 2014, and is under regulatory review in the EU. This article summarises the milestones in the development of oritavancin leading to this first approval for the treatment of ABSSSIs caused by Gram-positive bacteria.

A propensity score analysis shows that empirical treatment with linezolid does not increase the thirty-day mortality rate in patients with Gram-negative bacteremia.

The role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patients with Gram-negative bacteremia in the Hospital Clinic of Barcelona from 2000 to 2012 were included in this study. In order to compare the mortality rates between patients who received linezolid or glycopeptides, the propensity scores on baseline variables were used to balance the treatment groups, and both propensity score matching and propensity-adjusted logistic regression were used to compare the 30-day mortality rates between the groups. The overall 30-day mortality rate was 16.0% during the study period. Sixty-eight patients received empirical treatment with linezolid, and 1,058 received glycopeptides. The propensity score matching included 64 patients in each treatment group. After matching, the mortality rates were 14.1% (9/64) in patients who received glycopeptides and 21.9% (14/64) in those who received linezolid, and a nonsignificant association between empirical linezolid treatment and mortality rate (odds ratio [OR], 1.63; 95% confidence interval [CI], 0.69 to 3.82; P = 0.275, McNemar's test) was found. This association remained nonsignificant when variables that remained unbalanced after matching were included in a conditional logistic regression model. Further, the stratified propensity score analysis did not show any significant relationship between empirical linezolid treatment and the mortality rate after adjustment by propensity score quintiles or other variables potentially associated with mortality. In conclusion, the propensity score analysis showed that empirical treatment with linezolid compared with that with glycopeptides was not associated with 30-day mortality rates in patients with Gram-negative bacteremia.

Daptomycin plus trimethoprim/sulfamethoxazole combination therapy in post-neurosurgical meningitis caused by linezolid-resistant Staphylococcus epidermidis.

Post-neurosurgical infection is a serious complication that occurs in approx. 4% of all patients undergoing neurosurgical procedures and is associated with high morbidity and mortality rates and prolonged length of intensive care unit (ICU) stay. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are the most frequent pathogens involved in CNS post-neurosurgical meningitis. Treatment is challenging especially in patients with meningitis due to multidrug- resistant (MDR) CONS. Herein, we report a unique case of post-neurosurgical meningitis due to MRSE resistant to linezolid (a molecular analysis revealed the presence of the mutation G2576T on domain V of the 23S rRNA gene) and with reduced susceptibility to glycopeptides, successfully treated with a combination of daptomycin at 10 mg/kg daily plus trimethoprim/sulfamethoxazole (TMP/SMX). This antibiotic combination showed an indifferent interaction in in vitro studies. Daptomycin serum and cerebrospinal fluid (CSF) concentrations, determined through blood and CSF samples drawn just prior to and 4 h after the third dose, were 18.9-0.78 and 51.65-3.1 mg/L, respectively. These values allowed us to approximate a 5-6% penetration rate of the drug through an inflamed blood-brain barrier. In conclusion, although further studies are needed, combination of high-dose daptomycin plus TMP/SMX is a reasonable option for treatment of meningitis caused by multidrug-resistant S. epidermidis.

[Emergence of glycopeptide resistant Enterococcus faecium in Algeria: a case report]. / Émergence d'Enterococcus faecium résistant aux glycopeptides en Algérie : à propos d'un cas.

A glycopeptide-resistant Enterococcus faecium (EFRG) was isolated from a wound in a patient hospitalized in a university hospital in Algiers. This strain was resistant to several antibiotics. This patient was carrying this strain in the digestive tract which may partly explain its origin. Genotypic comparison of the two strains by pulsed field gel electrophoresis showed that it was the same strain. Glycopeptide resistance was due to the presence of the vanA gene. Vigilance is required facing the emergence of strains of EFRG in our hospitals.