- Characterisation of drug-specific signalling between primary human hepatocytes and immune cells. [Journal Article]
- TSToxicol Sci 2017 Apr 21
- It is now apparent that antigen-specific T-cells are activated in certain patients with drug-induced liver injury (DILI). Since cross-talk between hepatocytes and immune cells is likely to be critica...
It is now apparent that antigen-specific T-cells are activated in certain patients with drug-induced liver injury (DILI). Since cross-talk between hepatocytes and immune cells is likely to be critical in determining the outcome of drug exposure, the aim of this study was to profile the signals released by drug-treated hepatocytes and to characterise the impact of these molecules on dendritic cells. Human hepatocytes were exposed to three drugs (flucloxacillin, amoxicillin and isoniazid) associated with DILI potentially mediated by the adaptive immune system as drug-specific T-cells have been isolated from DILI patients, and the metabolite nitroso-sulfamethoxazole (SMX-NO). Hepatocyte toxicity, cytokine release and activation of oxidative stress pathways were measured. Supernatants were transferred to monocyte-derived dendritic cells and cell phenotype and function were assessed. High-mobility group box 1 protein (HMGB1) and lactate dehydrogenase release as well as adenosine triphosphate depletion occurred in a drug-, time- and concentration-dependent manner with SMX-NO and flucloxacillin, whereas isoniazid and amoxicillin were non-toxic. Furthermore, drug-induced activation of Nrf2 marker genes was observed when hepatocytes were exposed to test drugs. The disulphide isoform of HMGB1 stimulated dendritic cell cytokine release and enhanced the priming of naive T cells. Incubation of dendritic cells with supernatant from drug-treated hepatocytes resulted in two distinct cytokine profiles. SMX-NO/flucloxacillin stimulated secretion of TNF-á, IL-6, IL-1á and IL-1-â. Isoniazid which did not induce significant hepatocyte toxicity, compared with SMX-NO and flucloxacillin, stimulated the release of a panel of cytokines including the above and IFN-γ, IL-12, IL-17A, IP-10 and IL-10. Collectively, our study identifies drug-specific signalling pathways between hepatocytes and immune cells that could influence whether drug exposure will result in an immune response and tissue injury.
- Changes in Bacterial Resistance Patterns of Pediatric Urinary Tract Infections in İstanbul and Rationale for Empirical Antibiotic Therapy. [Journal Article]
- BMBalkan Med J 2017 Apr 06
- CONCLUSIONS: In childhood UTI, antibiotic resistance should be evaluated periodically and empiric antimicrobial therapy should be decided according to antibiotic sensitivity results.
- Identification of mycobacterial genes involved in antibiotic sensitivity - Implications in the treatment of tuberculosis with β-lactam containing regimens. [Journal Article]
- AAAntimicrob Agents Chemother 2017 Apr 24
- In a Mycobacterium smegmatis mutant library screen, transposon mutants with insertions in fhaA, dprE2, rpsT and parA, displayed hypersusceptibility to antibiotics including the β-lactams meropenem, a...
In a Mycobacterium smegmatis mutant library screen, transposon mutants with insertions in fhaA, dprE2, rpsT and parA, displayed hypersusceptibility to antibiotics including the β-lactams meropenem, ampicillin, amoxicillin and cefotaxime. Sub MIC levels of octoclothepin, a psychotic drug inhibiting ParA, phenocopied the parA insertion and enhanced the bactericidal activity of meropenem against Mycobacteriumtuberculosis in combination with clavulanate. Our study identifies novel factors associated with antibiotic resistance, with implications in repurposing β-lactams for tuberculosis treatment.
- Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media. [Journal Article]
- AAAntimicrob Agents Chemother 2017 Apr 24
- Amoxicillin/clavulanate (A/C), is currently the most effective oral antimicrobial in treating children with acute otitis media (AOM), but standard dosage of 90/6.4 mg/kg/day commonly causes diarrhea....
Amoxicillin/clavulanate (A/C), is currently the most effective oral antimicrobial in treating children with acute otitis media (AOM), but standard dosage of 90/6.4 mg/kg/day commonly causes diarrhea. We examined whether an A/C formulation containing lower concentrations of clavulanate would result in less diarrhea, while maintaining plasma levels of amoxicillin and clavulanate adequate to eradicate middle-ear pathogens and achieve clinical success. We conducted an open-label study in children aged 6 to 23 months with AOM. In Phase 1, we treated 40 children with a reduced-clavulanate A/C formulation providing 90/3.2 mg/kg/day for 10 days. In Phase 2, we treated 72 children with the same formulation at a dosage of 80/2.85 mg/kg/day for 10 days. We compared these children's rates of protocol-defined diarrhea (PDD), diaper dermatitis, and AOM clinical response with rates we had reported in children who received the standard A/C regimen, and we obtained plasma levels of amoxicillin and clavulanate at various time points. Outcomes in Phase 1 children and in children who had received the standard regimen did not differ significantly. Rates of PDD in children receiving Phase 2 and standard regimens were 17% and 26%, respectively (P=0.10). Corresponding rates of diaper dermatitis were 22% and 34% (P=0.04), and of AOM treatment failure were 12% and 16% (P=0.44). Symptomatic responses did not differ significantly between regimens; both gave clavulanate levels sufficient to inhibit β-lactamase activity. In young children with AOM, clavulanate dosages lower than those currently used may be associated with fewer side-effects without reducing clinical efficacy.
- Genome adaptive evolution of Lactobacillus casei under long-term antibiotic selection pressures. [Journal Article]
- BGBMC Genomics 2017 Apr 24; 18(1):320
- CONCLUSIONS: Our study has shown that the probiotic species, L. casei Zhang, has high genome stability even in the presence of long-term antibiotic stresses. However, whether this is a species-specific or universal characteristic for all probiotic bacteria remains to be explored.
- Antibiotic therapy for pelvic inflammatory disease. [Review]
- CDCochrane Database Syst Rev 2017 Apr 24; 4:CD010285
- CONCLUSIONS: We found no conclusive evidence that one regimen of antibiotics was safer or more effective than any other for the cure of PID, and there was no clear evidence for the use of nitroimidazoles (metronidazole) compared to use of other drugs with activity over anaerobes. Moderate-quality evidence from a single study at low risk of bias suggested that a macrolide (azithromycin) may be more effective than a tetracycline (doxycycline) for curing mild-moderate PID. Our review considered only the drugs that are currently used and mentioned by the CDC.
- Multidrug Resistance Salmonella Genomic Island 1 in a Morganella morganii subsp. morganii Human Clinical Isolate from France. [Journal Article]
- MmSphere 2017 Mar-Apr; 2(2)
- Salmonella genomic island 1 (SGI1) is a multidrug resistance integrative mobilizable element that harbors a great diversity of antimicrobial resistance gene clusters described in numerous Salmonella ...
Salmonella genomic island 1 (SGI1) is a multidrug resistance integrative mobilizable element that harbors a great diversity of antimicrobial resistance gene clusters described in numerous Salmonella enterica serovars and also in Proteus mirabilis. A serious threat to public health was revealed in the recent description in P. mirabilis of a SGI1-derivative multidrug resistance island named PGI1 (Proteus genomic island 1) carrying extended-spectrum-β-lactamase (ESBL) and metallo-β-lactamase resistance genes, blaVEB-6 and blaNDM-1, respectively. Here, we report the first description of Salmonella genomic island 1 (SGI1) in a multidrug-resistant clinical Morganella morganii subsp. morganii strain isolated from a patient in France in 2013. Complete-genome sequencing of the strain revealed SGI1 variant SGI1-L carrying resistance genes dfrA15, floR, tetA(G), blaPSE-1 (now referred to as blaCARB-2), and sul1, conferring resistance to trimethoprim, phenicols, tetracyclines, amoxicillin, and sulfonamides, respectively. The SGI1-L variant was integrated into the usual chromosome-specific integration site at the 3' end of the trmE gene. Beyond Salmonella enterica and Proteus mirabilis, the SGI1 integrative mobilizable element may thus also disseminate its multidrug resistance phenotype in another genus belonging to the Proteae tribe of the family Enterobacteriaceae. IMPORTANCE Since its initial identification in epidemic multidrug-resistant Salmonella enterica serovar Typhimurium DT104 strains, several SGI1 variants, SGI1 lineages, and SGI1-related elements (SGI2, PGI1, and AGI1) have been described in many bacterial genera (Salmonella, Proteus, Morganella, Vibrio, Shewanella, etc.). They constitute a family of multidrug resistance site-specific integrative elements acquired by horizontal gene transfer, SGI1 being the best-characterized element. The horizontal transfer of SGI1/PGI1 elements into other genera is of public health concern, notably with regard to the spread of critically important resistance genes such as ESBL and carbapenemase genes. The identification of SGI1 in Morganella morganii raises the issue of (i) the potential for SGI1 to emerge in other human pathogens and (ii) its bacterial host range. Further surveillance and research are needed to understand the epidemiology, the spread, and the importance of the members of this SGI1 family of integrative elements in contributing to antibiotic resistance development.
- Aerococcus urinae: An Emerging Cause of Urinary Tract Infection in Older Adults with Multimorbidity and Urologic Cancer. [Journal Article]
- UCUrol Case Rep 2017; 13:24-25
- Aerococcus urinae is a rare organism isolated from urine cultures. We present a case of an 80 year-old male with bladder cancer and multimorbidity who developed A. urinae infection. A. urinae may cau...
Aerococcus urinae is a rare organism isolated from urine cultures. We present a case of an 80 year-old male with bladder cancer and multimorbidity who developed A. urinae infection. A. urinae may cause simple and complicated UTIs, bacteremia, and endocarditis in older adults with multimorbidity, chronic urinary retention, or indwelling catheters. A. urinae treatment should employ penicillin, amoxicillin, and nitrofurantoin. Due to increasing antibiotic resistance, urine culture should include antibiotic susceptibility testing. Prompt and culture-specific treatment is critical to avoid clinical progression of the infection.
- Phenotypic and genotypic characterization of methicillin-resistant Staphylococcus aureus from bovine mastitis. [Journal Article]
- VWVet World 2017; 10(3):363-367
- CONCLUSIONS: The higher occurrence of S. aureus-mediated mastitis was concluded due to improper hygienic and poor farm management. The multiple drug resistance reveals the indiscriminate use of drugs and presence of methicillin resistance gene determinant is an alarming situation as such infections are difficult to treat.
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- Occurrence of multidrug resistant Escherichia coli in groundwater of Brij region (Uttar Pradesh) and its public health implications. [Journal Article]
- VWVet World 2017; 10(3):293-301
- CONCLUSIONS: Groundwater is considered to be a safe option for potable water but it is obvious from the findings of this study that considerable physicochemical and microbial contamination is there in groundwater samples of Brij region. The occurrence of MDR E. coli in these waters is a matter of great public health concern.