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Background The transition from colonization to invasion is critical in diabetic foot ulcer (DFU). Staphylococcus aureus can colonize DFU, or invade the underlying tissues, causing serious infections. The ROSA-like prophage has previously been implicated in strain colonization characteristics of S aureus isolates in uninfected ulcers. Methods In this study, we investigated this prophage in the S aureus -colonizing strain using an in vitro chronic wound medium mimicking the chronic wound environment. Results Chronic wound medium reduced bacterial growth and increased biofilm formation and virulence in a zebrafish model. Conclusions The ROSA-like prophage promoted intracellular survival of S aureus -colonizing strain in macrophages, keratinocytes, and osteoblasts. [ABSTRACT FROM AUTHOR]

Background Diabetic foot infections (DFIs) represent a public health problem because of their frequency and the severity of their consequences, i.e. amputation and mortality. Polymicrobial biofilms on the skin surface of these ulcers complicate wound healing. Few in vitro models exist to study the antibiotics activity in this context. Objectives This study evaluated the in vitro activity of antibiotics against the two main bacteria isolated in DFI, Staphylococcus aureus and Pseudomonas aeruginosa , using a dynamic system (BioFlux™ 200) and a chronic wound-like medium (CWM) that mimic the foot ulcer environment. Methods Reference strains and two pairs of clinical S. aureus and P. aeruginosa isolated together from a DFI were cultivated in brain heart infusion and CWM media during 72 h at 37°C, alone and combined in the BioFlux™ 200 system. Antibiotic activity was evaluated after a mechanical debridement. The activities were measured by the reduction of biofilm percentage of bacteria in the microfluidic system using microscopy. Results Daptomycin for S. aureus and ceftazidime for P. aeruginosa showed excellent activity to reduce biofilm biomass, whereas linezolid action was more mitigated and dalbavancin was ineffective. Ceftazidime + daptomycin presented the most potent in vitro activity on a mixed biofilm. Conclusions The combination of CWM and the BioFlux™ microfluidic system represents a valuable tool to screen the potential antimicrobial activity of antibiotics under conditions mimicking those encountered in DFI. It could help clinicians in their management of chronic wounds. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot infections (DFIs) represent a serious threat to public health because of their frequency and the severity of their consequences, i.e. osteomyelitis and amputation. The management of diabetic foot osteomyelitis (DFOM) requires prolonged antibiotic therapy. In Western countries, Gram-positive bacteria are the most commonly encountered pathogens.Objectives: This study evaluated the in vitro activity of dalbavancin, a novel lipoglycopeptide with extended half-life, recently marketed in Europe for acute bacterial skin and skin structure infections, on a panel of Gram-positive bacteria responsible for DFOM.Methods: Dalbavancin activity was evaluated against a panel of Gram-positive bacterial strains isolated from bone biopsies performed by a trained surgeon among patients with suspected DFOM. MICs were determined using MIC Test Strips (Liofilchem) and confirmed with the EUCAST broth microdilution method. Three other antimicrobial agents (vancomycin, teicoplanin and ceftobiprole) were used as comparators.Results: Dalbavancin showed excellent activity against all Gram-positive bacterial strains tested, including one teicoplanin-resistant Staphylococcus epidermidis isolate. With MIC50 and MIC90 values of 0.047 and 0.094 mg/L, respectively, dalbavancin showed the most potent in vitro activity among antimicrobial agents tested.Conclusions: With its efficacy, good tolerability and unique pharmacokinetic properties, dalbavancin appears to be a promising treatment for DFOM involving Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

We report the first case of brucellosis caused by an isolate whose genome is identical that of a frog isolate from Texas, demonstrating the zoonotic potential of amphibian-type Brucella. Importantly, with such atypical Brucella , correct diagnosis cannot be performed using routine serological tests or identification methods. [ABSTRACT FROM AUTHOR]

Background Recurrent urinary tract infections (R-UTIs) are the main cause of morbidity and hospitalizations in subjects with neurogenic bladder (NB) due to spinal cord injury (SCI). We evaluated the efficacy of weekly oral cyclic antibiotic (WOCA) prophylaxis (ie, the alternate weekly administration of 2 antibiotics) in preventing R-UTIs. Methods Randomized (1:1), open-label, superiority-controlled trial compared WOCA prophylaxis to no prophylaxis (control) for 6 months in patients with NB due to SCI, using clean intermittent self-catheterization, and suffering from R-UTIs. Primary outcome was incidence of symptomatic antibiotic-treated UTIs. Secondary outcomes were number of febrile UTIs, number of hospitalizations, WOCA tolerance, antibiotic consumption, number of negative urine cultures, and emergence of bacterial resistance in urinary, intestinal, and nasal microbiota. Results Forty-five patients were either allocated to the WOCA group (n = 23) or the control group (n = 22). Median (IQR) incidence of symptomatic antibiotic-treated UTIs was 1.0 (0.5–2.5) in the WOCA group versus 2.5 (1.2–4.0) (P =.0241) in the control group. No febrile UTIs were recorded in the WOCA group versus 9 (45.0%) (P <.001) in the control group. The median number of additional antibiotic treatment was 0.0 (IQR, 0.0–2.0) versus 3.0 (2.0–5.0) (P =.004) in the WOCA and control groups, respectively. Only few adverse events were reported. No impact on emergence of bacterial resistance was observed. Conclusions WOCA is efficient and well tolerated in preventing R-UTIs in SCI patients. In our study, we did not observe any emergence of antibiotic resistance in digestive and nasal microbiological cultures. Clinical Trials Registration NCT01388413. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prevalence and molecular characteristics of OXA-48-carbapenemase-producing Enterobacterales strains recovered from various ecological niches in Algeria.Methods: In total, 3309 samples were collected from different ecological niches (human carriage, animal farms, wild animals, pets, food products, aquatic environment and wastewater treatment plants) distributed among six provinces in Algeria between December 2015 and April 2017. The potential presence of OXA-48-producing Enterobacterales isolates was screened on selective medium. Resistance and virulence profiles were characterized by PCR and sequencing. The clonal relatedness of the different isolates was studied using Rep-PCR and MLST. Conjugation was performed for all OXA-48-producing isolates. The plasmids were analysed by PCR-based replicon typing and WGS.Results: A total of 78 OXA-48-producing Enterobacterales isolates were detected from 3309 samples (2.4%). OXA producers were observed in all the screened sources. The blaCTX-M-15 gene was only observed in two isolates. Clonality analysis revealed distinct lineages of the isolates and a clonal expansion of Klebsiella pneumoniae ST13. K. pneumoniae and Escherichia coli had few virulence factors. Plasmid analysis confirmed that all the isolates harboured a very similar transferable plasmid (belonging to IncL) with a similar structure to the pOXA-48a plasmid carried by K. pneumoniae strain Kp11978.Conclusions: This study suggests a global dissemination of OXA-48-producing Enterobacterales in different niches due mainly to the spread of an epidemic plasmid. Furthermore, it clearly shows that K. pneumoniae and commensal E. coli can be reservoirs of the blaOXA-48 gene, contributing to the dissemination and transfer of this gene to diverse bacteria among different sources. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the performance of the Accelerate Pheno™ system for the identification and antimicrobial susceptibility testing (AST) of a panel of Gram-negative bacilli (GNB) with different resistance profiles (e.g. penicillinases, ESBLs, cephalosporinase overproduction, carbapenemases, impermeability) directly from positive blood cultures in <7 h.Methods: A panel of 105 clinical strains previously characterized for the presence of β-lactamase-encoding genes was tested. Approximately 100 cfu of each isolate was inoculated into sterile blood culture bottles and incubated in a BD BACTEC™ FX automated system (Becton Dickinson, USA). Positive blood cultures were subjected to parallel testing using the Accelerate Pheno™ system and conventional culture methods [identification of isolated colonies by MALDI-TOF and VITEK® 2 system (bioMérieux, France), and AST by disc diffusion and Etest following EUCAST recommendations].Results: The overall identification agreement between the Accelerate Pheno™ system and conventional culture methods was 100% (105/105). The overall categorical agreement between the system and culture-based AST was 94.9% (1169/1232), with rates for minor errors of 4.1% (51/1232), major errors 0.3% (4/1232) and very major errors 0.7% (8/1232). The Accelerate Pheno™ system produced AST results indicative of third-generation cephalosporinases (26/26) and carbapenem-resistant strains (52/55).Conclusions: The Accelerate Pheno™ system is an accurate, sensitive and easy-to-use test for the rapid identification and AST of MDR GNB in bloodstream infections. Given the burden of multidrug resistance, its implementation in the microbiology laboratory could be a useful tool for prompt management of sepsis. [ABSTRACT FROM AUTHOR]

The mechanisms that drive the transition from commensality to invasiveness in Staphylococcus aureus are poorly understood. We recently reported that >50% of S. aureus isolates from uninfected diabetic foot ulcers in French patients harbor a prophage, ROSA-like, that is absent from invasive isolates from diabetic foot infections, including osteomyelitis. Here we show that the ROSA-like insertion abolishes the ability of S. aureus to replicate within osteoblasts, the bone-forming cells, greatly reducing damage to infected cells. These results unravel an important mechanism by which particular S. aureus strains are maintained in a commensal state in diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

Objectives: Low first-dose peak serum concentrations of amikacin and gentamicin are commonly reported in ICU patients. The present study aimed to assess whether 30 mg/kg amikacin or 8 mg/kg gentamicin achieved target concentrations in ICU patients with severe sepsis.Patients and Methods: Sixty-three ICU patients (Simplified Acute Physiology Score II = 43 ± 16) with severe sepsis and an indication for intravenous amikacin (n = 47) or gentamicin (n = 16) were included. The first (30 mg/kg amikacin; 8 mg/kg gentamicin) and subsequent doses and corresponding peak concentrations (30 min after the completion of an infusion) were recorded. French guideline target concentrations were ≥60 and ≥30 mg/L for amikacin and gentamicin, respectively. A target pharmacokinetic/pharmacodynamic ratio of 10 × MIC was also measured.Results: Pulmonary, abdominal and urinary tract infections were diagnosed in 56 patients. Infection was confirmed in 37 patients (59%). The targeted first-dose peak concentration was achieved in 37/63 patients (59%) [amikacin 36/47 (77%) and gentamicin 1/16 (6%)], and 59/63 patients (94%) achieved the pharmacokinetic/pharmacodynamic ratio using the MIC data that were available from 21 patients. However, the second dose of aminoglycoside was withheld because of high trough concentrations in nearly half of patients who did not have renal dysfunction.Conclusions: In this study, 30 mg/kg amikacin and 8 mg/kg gentamicin led to target peak serum concentrations in 59% of patients. [ABSTRACT FROM AUTHOR]

Objectives To determine the prevalence of multidrug-resistant (MDR) Gram-negative bacilli and extended spectrum β-lactamase (ESBL)-producing isolates in stool specimens obtained from patients hospitalized for acute diarrhoea in a French university hospital. Methods Bacteria in stool specimens were screened for ESBL production on Drigalski agar supplemented with ceftazidime, ESBL CHROMagar® and CTX CHROMagar® media and confirmed by the double-disc synergy test. Genetic detection was performed by PCR and sequencing with bacterial DNA extracted from isolates. Results The presence of MDR bacteria was markedly high (96 of 303 patients, 31.7%). The majority of MDR bacteria were Enterobacter cloacae (44, 38%) and Escherichia coli (32, 28%). Moreover, the prevalence of ESBL and CTX-M producers among all included patients was 15.8% and 5.9%, respectively. The clone E. coli O25b : H4-ST131 was detected in 63% of CTX-M strains. Surprisingly, 16 carbapenemases (5.3% of patients) were isolated. Conclusions The study revealed the wide dissemination of MDR bacteria, including carbapenemase producers, in a French hospital during a non-outbreak situation. Public health efforts to combat emergence and dissemination of MDR organisms need to be developed. [ABSTRACT FROM PUBLISHER]

Background: Concomitant with the recent emergence of CTX-M-type extended-spectrum beta-lactamases (ESBLs), Escherichia coli has become the enterobacterial species most affected by ESBLs. Multiple locales are encountering CTX-M-positive E. coli, including specifically CTX-M-15. To gain insights into the mechanism underlying this phenomenon, we assessed clonality and diversity of virulence profiles within an international collection of CTX-M-15-positive E. coli.Methods: Forty-one ESBL-positive E. coli isolates from eight countries and three continents (Europe, Asia and North America) were selected for study based on suspected clonality. Phylogenetic group, ERIC2 PCR profile, O H serotype, AmpC variant and antibiotic susceptibility were determined. Multilocus sequence typing (MLST) and PFGE provided additional discrimination. Virulence potential was inferred by detection of 46 virulence factor (VF) genes.Results: Thirty-six (88%) of the 41 E. coli isolates exhibited the same set of core characteristics: phylogenetic group B2, ERIC2 PCR profile 1, serotype O25:H4, AmpC EC6, ciprofloxacin resistance and MLST profile ST131. By PFGE, the 36 isolates constituted one large cluster at the 68% similarity level; this comprised 17 PFGE groups (defined at 85% similarity), some of which included strains from different countries. The 36 isolates exhibited highly (91% to 100%) similar VF profiles.Conclusions: We describe a broadly disseminated, CTX-M-15-positive and virulent E. coli clonal group with highly homogeneous virulence genotypes and subgroups exhibiting highly similar PFGE profiles, suggesting recent emergence. Understanding how this clone has emerged and successfully disseminated within the hospital and community, including across national boundaries, should be a public health priority. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study on the use of squalamine as a chemosensitizer to prevent antibiotic-resistant gram-negative bacteria. According to the authors, the effect of squalamine on bacterial strains devoid of porin showed an increase in penetration for cefepime and ciprofloxacin. They add that squalamine allows an increase in bacterial susceptibility when the mechanical barrier, restricted uptake or efficient efflux pump are involved in resistance.