- Population pharmacokinetic modeling to establish the role of P-glycoprotein on ciprofloxacin distribution to lung and prostate following intravenous and intratracheal administration to Wistar rats. [Journal Article]
- EJEur J Pharm Sci 2018 Nov 10
- Ciprofloxacin (CIP) is indicated for clinical treatment of urinary and respiratory tract infections. Poor infection site penetration and consequent insufficient exposure to the antimicrobial agent ma...
Ciprofloxacin (CIP) is indicated for clinical treatment of urinary and respiratory tract infections. Poor infection site penetration and consequent insufficient exposure to the antimicrobial agent may be the reason for some therapeutic failures. Ciprofloxacin is reported as a substrate for efflux transporters, such as P-glycoprotein, which could be related to the presence of sub-therapeutic drug concentration at the infection site. In the present work we evaluated CIP pharmacokinetics (PK) in plasma and lung and prostate tissues of Wistar rats after intravenous (i.v.) and intratracheal (i.t.) dosing (7 mg/Kg) in the presence and absence of P-gp inhibitor tariquidar (TAR, 15 mg/Kg). Microdialysis was applied to determine free tissue concentration-time profiles and the obtained data were analyzed by non-compartmental and population PK (popPK) analysis. A sequential strategy was used to develop the popPK model: characterization of CIP PK in tissues (Tissue model) was performed subsequently to CIP PK modeling in plasma (Plasma model). Two and three compartmental models were used to simultaneously characterize plasma concentrations after i.t. and i.v. dosing; the distribution model was developed by separating the central compartment into venous and arterial compartment and by adding lung and prostate; TAR was identified as a significant covariate for clearance and volume of distribution of central compartment as well as for inter-compartmental clearance. Our results indicate an impact of P-gp on plasma PK, likely by acting on renal active secretion of CIP. Regarding CIP exposure in lung and prostate tissues, our results suggest a complex interplay between drug transporters; P-gp inhibition by TAR was likely counterbalanced by the activity of other efflux/influx transporters, which could not be fully characterized by our model.
- Hypothermia in Young Infants: Frequency and Yield of Sepsis Workup. [Journal Article]
- PEPediatr Emerg Care 2018 Nov 12
- CONCLUSIONS: Approximately a quarter of infants younger than 60 days with hypothermia were evaluated for SBI. Serious bacterial infection was identified in 9% of evaluated infants (2% of all hypothermic infants). Hypothermia can be a presenting sign of SBI.
- Nursing resources and major immobility complications among bedridden patients: a multicenter descriptive study in China. [Journal Article]
- JNJ Nurs Manag 2018 Nov 13
- CONCLUSIONS: Sufficient nurse staffing and higher professional titles of nurses might contribute to reducing the incidence of major immobility complications. Nurse experience was not related to the incidence of major immobility complications. However, the association between nurse education level and the incidence of major immobility complications requires further investigation. This article is protected by copyright. All rights reserved.
- Molecular analysis of uropathogenic E.coli isolates from Urinary tract infections in Ilam. [Journal Article]
- IDInfect Disord Drug Targets 2018 Nov 12
- The aim of the current study was to investigate the prevalence virulence genes profile in UPEC isolates in Ilam. For this purpose, a total of 8o UPEC isolates for patients with UTIs were collected du...
The aim of the current study was to investigate the prevalence virulence genes profile in UPEC isolates in Ilam. For this purpose, a total of 8o UPEC isolates for patients with UTIs were collected during 6 months period. The multiplex polymerase chain reaction (Multiplex PCR) was used for detection of the papEF, fimH, iucD, hlyA, fyuA, and ompT genes. The prevalence of genes the fimH, papEF, iucD, fyuA, hlyA, hlyA and ompT were 87.5, 47.5, 60, 67.5, 27.5, 47.5 and 71.2, respectively. Among all of isolates, 27 gene profiles were obtained. The number isolates related to 4 virulence factor simultaneous that were 25 isolates. Considering the different antibiotic patterns, will be proposed develop and an appropriate program for antibiotics in each region and even in each hospital. Also, investigation about the profile of different virulence genes which capable of inducing various pathogens is will be done in the future.
- Evaluation of MALDI-TOF VITEK®MS and VITEK® 2 system for the identification of Staphylococcus saprophyticus. [Journal Article]
- FMFuture Microbiol 2018 Nov 13
- CONCLUSIONS: MALDI-TOF VITEK®MS is more accurate than the automated VITEK® 2 system in identifying CoNS isolated from urinary tract infections to species level, particularly urinary isolates of S. saprophyticus.
- Higher Prevalence of PldA, a Pseudomonas aeruginosa Trans-Kingdom H2-Type VI Secretion System Effector, in Clinical Isolates Responsible for Acute Infections and in Multidrug Resistant Strains. [Journal Article]
- FMFront Microbiol 2018; 9:2578
- Pseudomonas aeruginosa can manipulate eukaryotic host cells using secreted effectors delivered by the type III or the type VI Secretion Systems (T3SS and T6SS). The T3SS allows the injection of bacte...
Pseudomonas aeruginosa can manipulate eukaryotic host cells using secreted effectors delivered by the type III or the type VI Secretion Systems (T3SS and T6SS). The T3SS allows the injection of bacterial effectors (Exo toxins) into eukaryotic cell. P. aeruginosa, encodes three T6SSs, H1-, H2- and H3-T6SS. The H1-T6SS is mainly involved in delivering toxins to kill bacterial competitors. Recently, two T6SS-secreted phospholipases D, PldA (H2-T6SS) and PldB (H3-T6SS), were identified as trans-kingdom virulence effectors, triggering both killing of bacterial competitors and internalization into non-phagocytic cells. We deciphered the prevalence of T3SS and T6SS effectors encoding genes in 185 clinical isolates responsible for infections (septicaemia, pulmonary infections, urinary tract infections, and chronic infections in CF patients), 47 environmental strains, and on 33 carbapenemase-producers. We included 107 complete genomes of P. aeruginosa available in public databases. The prevalence of pldA is increased in clinical isolates responsible for severe acute infection and particularly in multi-drug resistant strains. In contrast, the pldB prevalence was high (96.8%) in all isolates. Regarding T3SS effectors, exoT and exoY are present in nearly all isolates while exoS and exoU were found to be exclusive with a higher prevalence of exoU+ strains in severe acute infections. The hypervirulent exoU+ isolates are more prone to be pldA+, suggesting a role of PldA in virulence. Finally, we observed that extremely drug resistant isolates producing an IMP-type carbapenemase were all pldA+. Our results suggest that PldA might have a role during pulmonary infections and have been co-selected in multidrug resistant strains particularly IMP-producers.
- The efficacy and safety of tazobactam/ceftolozane in Japanese patients with uncomplicated pyelonephritis and complicated urinary tract infection. [Journal Article]
- JIJ Infect Chemother 2018 Nov 09
- We report efficacy and safety results for a combination of a novel cephalosporin class antibiotic and a β-Lactamase inhibitor, tazobactam/ceftolozane (1:2) at a dose of 1.5 g intravenously every 8 h ...
We report efficacy and safety results for a combination of a novel cephalosporin class antibiotic and a β-Lactamase inhibitor, tazobactam/ceftolozane (1:2) at a dose of 1.5 g intravenously every 8 h in Japanese patients with uncomplicated pyelonephritis and complicated urinary tract infection. This study design was a nonrandomized, multicenter, open-label trial, and the treatment period was 7 days. Of 115 patients enrolled in this study, 114 received tazobactam/ceftolozane, and 90 were included in the efficacy analyses. Ninety-nine isolates (bacterial count ≥105 CFU/mL) were identified by urine culture. The main baseline uropathogens were Escherichia coli (80 isolates), Klebsiella pneumoniae (8 isolates), and Proteus mirabilis (3 isolates). Of these, 13 isolates were ESBL-producers. The favorable per-patient microbiological response rate at 7 days after the final administration of tazobactam/ceftolozane was 80.7% (71/88). The response rate in uncomplicated pyelonephritis was 90.0% (36/40), complicated pyelonephritis 63.6% (14/22), and complicated cystitis 80.8% (21/26). The favorable clinical response rate was 96.6% (86/89), and composite response rate (based on microbiological and clinical response) was 80.7% (71/88). The eradication rate by uropathogen was 83.5% (66/79) in E. coli, 42.9% (3/7) in K. pneumoniae, and 100% (3/3) in P. mirabilis. The incidence of drug-related adverse events was 17.5% (20/114 patients). The most common drug-related adverse events were diarrhea and alanine aminotransferase increased in 5.3% (6/114 patients each). Drug-related serious adverse events and deaths were not observed. These results support the safety and efficacy of tazobactam/ceftolozane and suggest it will be a useful treatment for uncomplicated pyelonephritis and complicated urinary tract infection.
- Surgical outcomes of infectious spondylitis after vertebroplasty, and comparisons between pyogenic and tuberculosis. [Journal Article]
- BIBMC Infect Dis 2018 Nov 12; 18(1):555
- CONCLUSIONS: Infection spondylitis after VP required major surgery for salvage with a relevant part of residual disability. Before VP, any bacteremia/UTI or history of pulmonary TB should be reviewed rigorously; any elevation of infection parameters should be scrutinized strictly.
- Reliability of Symptom-Based Diagnosis of Uncomplicated Cystitis. [Journal Article]
- UIUrol Int 2018 Nov 12; :1-13
- CONCLUSIONS: The severity of the symptom is even more essential than just its presence for an accurate diagnosis. The ACSS is an accurate tool and may be recommended for clinical practice and studies for diagnosis of AC in women. Further studies and unification of terms are need.
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- Quorum quelling efficacy of marine cyclic dipeptide -cyclo(L-leucyl-L-prolyl) against the uropathogen Serratia marcescens. [Journal Article]
- FCFood Chem Toxicol 2018 Nov 09
- In the current study, the anti-QS efficacy of cyclic dipeptide -cyclo(L-leucyl-L-prolyl) (CLP) of marine origin was explored against S. marcescens. Minimal -inhibitory (MIC) and -bactericidal concent...
In the current study, the anti-QS efficacy of cyclic dipeptide -cyclo(L-leucyl-L-prolyl) (CLP) of marine origin was explored against S. marcescens. Minimal -inhibitory (MIC) and -bactericidal concentrations (MBC) of CLP against both reference and a clinical isolate of S. marcescens was identified to be 200 and 400 μg/mL, respectively. CLP proficiently inhibited the QS controlled prodigiosin production in S. marcescens, which affirm its anti-QS efficacy towards S. marcescens. At sub-MICs (100 μg/mL), CLP exhibited a phenomenal inhibitory propensity towards the production of virulence traits viz. biofilm, exopolymeric substance, protease and lipase to the level of 81, 77, 71 and 92%, respectively. Further, the confocal and scanning electron microscopic analyses validated the antibiofilm efficacy of CLP. Besides, CLP effectively modified the hydrophobic and motility characteristics of S. marcescens. Furthermore, the in vivo assay using C. elegans revealed the non-toxic and anti-adherence propensity of CLP. Concomitantly, the down regulation of QS controlled virulence genes (unveiled through qPCR analysis) are in accordance with the data of phenotypic and in vivo assays. Therefore, this study exemplifies CLP could plausibly be a convincing alternative over conventional antibiotics in preventing the QS associated pathogenesis of uropathogens.