The effects of single and multiple resistance mechanisms on bacterial response to meropenem.

Objectives: Meropenem is commonly used against Pseudomonas aeruginosa. Traditionally, the time unbound antibiotic concentration exceeds the MIC (fT) is used to select carbapenem regimens. We aimed to characterize the effects of different baseline resistance mechanisms on bacterial killing and resistance emergence; evaluate whether fT can predict these effects; and, develop a novel Quantitative and Systems Pharmacology (QSP) model to describe the effects of baseline resistance mechanisms on the time-course of bacterial response.

'You are looked upon as a luxury tool': Young Tanzanian women's perception of community norms supporting partner violence during transactional sex ().

This paper explores the definition of, and perceived community attitudes, toward , a Swahili street term for a type of transactional sex practised in Dar es Salaam, Tanzania. Rooted in economic and gender disparity, transactional sex increases adolescent girls' and young women's vulnerability to HIV and gender-based violence. We sought to understand perceived community attitudes about kudanga, and how the internalisation of norms surrounding gender-based violence relate to the experiences of young women who practise kudanga.

Synergistic effects of inhaled aztreonam plus tobramycin on hypermutable cystic fibrosis Pseudomonas aeruginosa isolates in a dynamic biofilm model evaluated by mechanism-based modelling and whole genome sequencing.

Objective: Hypermutable Pseudomonas aeruginosa strains are highly prevalent in chronic lung infections of patients with cystic fibrosis (CF). Acute exacerbations of these infections have limited treatment options. This study aimed to investigate inhaled aztreonam and tobramycin against clinical hypermutable P.

Systematic review of cash plus or bundled interventions targeting adolescents in Africa to reduce HIV risk.

Background: HIV remains a leading cause of death for adolescents and young people aged 10-24 years. HIV prevention requires multisectoral approaches that target adolescents and young people, addressing HIV risk pathways (e.g.

The influence of gender-equitable attitudes on sexual behaviour among unmarried adolescents in rural Tanzania: a longitudinal study.

Gender norms that centre men and disadvantage women create gender inequality, which can lead to risky sexual behaviour. This study examined how both community and individual attitudes toward gender norms influenced risky sexual behaviour in adolescents, and whether that influence was different between males and females. We found that higher gender-equitable attitudes were linked to increased odds of HIV testing in the last 12 months, and decreased odds of engaging in a sexual relationship with a much older partner.

Ceftolozane-Tazobactam against Pseudomonas aeruginosa Cystic Fibrosis Clinical Isolates in the Hollow-Fiber Infection Model: Challenges Imposed by Hypermutability and Heteroresistance.

Pseudomonas aeruginosa remains a challenge in chronic respiratory infections in cystic fibrosis (CF). Ceftolozane-tazobactam has not yet been evaluated against multidrug-resistant hypermutable P. aeruginosa isolates in the hollow-fiber infection model (HFIM).

Ceftolozane/tazobactam plus tobramycin against free-floating and biofilm bacteria of hypermutable Pseudomonas aeruginosa epidemic strains: Resistance mechanisms and synergistic activity.

Objective: Acute exacerbations of biofilm-associated Pseudomonas aeruginosa infections in cystic fibrosis (CF) have limited treatment options. Ceftolozane/tazobactam (alone and with a second antibiotic) has not yet been investigated against hypermutable clinical P. aeruginosa isolates in biofilm growth.

Penicillin G concentrations required for prophylaxis against Group A Streptococcus infection evaluated using a hollow fibre model and mathematical modelling.

Background: Acute rheumatic fever (ARF), an autoimmune reaction to Group A Streptococcus (Streptococcus pyogenes; Strep A) infection, can cause rheumatic heart disease (RHD). New formulations of long-acting penicillins are being developed for secondary prophylaxis of ARF and RHD.

Objectives: To evaluate the penicillin G concentrations required to suppress growth of Strep A.

Effect of Different Piperacillin-Tazobactam Dosage Regimens on Synergy of the Combination with Tobramycin against for the Pharmacokinetics of Critically Ill Patients in a Dynamic Infection Model.

We evaluated piperacillin-tazobactam and tobramycin regimens against isolates from critically ill patients. Static-concentration time-kill studies (SCTK) assessed piperacillin-tazobactam and tobramycin monotherapies and combinations against four isolates over 72 h. A 120 h-dynamic in vitro infection model (IVM) investigated isolates Pa1281 (MIC 4 mg/L, MIC 0.

Retrospective Analysis of Clinical Outcomes Associated With the Use of Pegfilgrastim On-body Injector in Patients Receiving Chemotherapy Requiring Granulocyte Colony-Stimulating Factor Support.

Pegfilgrastim is a granulocyte colony-stimulating factor (G-CSF) used as primary prophylaxis in patients receiving myelosuppressive chemotherapy regimens that have greater than 20% risk of developing febrile neutropenia (FN). Historically, pegfilgrastim has been administered 24 to 72 hours after chemotherapy, necessitating a return to clinic to receive the provider-administered injection. An alternative option is the pegfilgrastim on-body injector (OBI).

Evaluation of Meropenem-Ciprofloxacin Combination Dosage Regimens for the Pharmacokinetics of Critically Ill Patients With Augmented Renal Clearance.

Augmented renal clearance (ARC, creatinine clearance > 130 mL/minute) makes difficult achievement of effective concentrations of renally cleared antibiotics in critically ill patients. This study examined the synergistic killing and resistance suppression for meropenem-ciprofloxacin combination dosage regimens against Pseudomonas aeruginosa isolates within the context of ARC. Clinically relevant meropenem and ciprofloxacin concentrations, alone and in combinations, were studied against three clinical isolates with a range of susceptibilities to each of the antibiotics.

Meropenem-Tobramycin Combination Regimens Combat Carbapenem-Resistant Pseudomonas aeruginosa in the Hollow-Fiber Infection Model Simulating Augmented Renal Clearance in Critically Ill Patients.

Augmented renal clearance (ARC) is common in critically ill patients and is associated with subtherapeutic concentrations of renally eliminated antibiotics. We investigated the impact of ARC on bacterial killing and resistance amplification for meropenem and tobramycin regimens in monotherapy and combination. Two carbapenem-resistant isolates were studied in static-concentration time-kill studies.

Association between the North Carolina Medical Board opioid guideline update and opioid prescriptions in Medicare Part D beneficiaries.

Objective: To examine if North Carolina (NC) opioid prescribing guidelines were associated with changes in opioid prescribing.

Method: Retrospective secondary analysis of the Medicare Provider Utilization and Payment Data: Part D Prescriber datasets from 2013 to 2015.

Participants: Providers who prescribed at least one opioid from 2013 to 2015 and paid by Medicare Part D.

Meropenem Combined with Ciprofloxacin Combats Hypermutable Pseudomonas aeruginosa from Respiratory Infections of Cystic Fibrosis Patients.

Hypermutable organisms are prevalent in chronic respiratory infections and have been associated with reduced lung function in cystic fibrosis (CF); these isolates can become resistant to all antibiotics in monotherapy. This study aimed to evaluate the time course of bacterial killing and resistance of meropenem and ciprofloxacin in combination against hypermutable and nonhypermutable Static concentration time-kill experiments over 72 h assessed meropenem and ciprofloxacin in mono- and combination therapies against PAO1 (nonhypermutable), PAOΔ (hypermutable), and hypermutable isolates CW8, CW35, and CW44 obtained from CF patients with chronic respiratory infections. Meropenem (1 or 2 g every 8 h [q8h] as 3-h infusions and 3 g/day as a continuous infusion) and ciprofloxacin (400 mg q8h as 1-h infusions) in monotherapies and combinations were further evaluated in an 8-day hollow-fiber infection model study (HFIM) against CW44.

Optimization and Evaluation of Piperacillin-Tobramycin Combination Dosage Regimens against Pseudomonas aeruginosa for Patients with Altered Pharmacokinetics via the Hollow-Fiber Infection Model and Mechanism-Based Modeling.

Augmented renal clearance (ARC) in critically ill patients can result in suboptimal drug exposures and treatment failure. Combination dosage regimens accounting for ARC have never been optimized and evaluated against by use of the hollow-fiber infection model (HFIM). Using a isolate from a critically ill patient and static-concentration time-kill experiments (SCTKs), we studied clinically relevant piperacillin and tobramycin concentrations, alone and in combinations, against two inocula (10 and 10 CFU/ml) over 72 h.

Optimization of a Meropenem-Tobramycin Combination Dosage Regimen against Hypermutable and Nonhypermutable Pseudomonas aeruginosa via Mechanism-Based Modeling and the Hollow-Fiber Infection Model.

Hypermutable strains are prevalent in patients with cystic fibrosis and rapidly become resistant to antibiotic monotherapies. Combination dosage regimens have not been optimized against such strains using mechanism-based modeling (MBM) and the hollow-fiber infection model (HFIM). The PAO1 wild-type strain and its isogenic hypermutable PAOΔ strain (MIC of 1.

Combating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem-plus-Tobramycin Dosage Regimen: Prospective Validation via Hollow-Fiber Infection and Mathematical Modeling.

We aimed to prospectively validate an optimized combination dosage regimen against a clinical carbapenem-resistant (CRAB) isolate (imipenem MIC, 32 mg/liter; tobramycin MIC, 2 mg/liter). Imipenem at constant concentrations (7.6, 13.

Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model.

Critically ill patients frequently have substantially altered pharmacokinetics compared to non-critically ill patients. We investigated the impact of pharmacokinetic alterations on bacterial killing and resistance for commonly used meropenem dosing regimens. A isolate (MIC 0.

Effect of different renal function on antibacterial effects of piperacillin against Pseudomonas aeruginosa evaluated via the hollow-fibre infection model and mechanism-based modelling.

Background: Pathophysiological changes in critically ill patients can cause severely altered pharmacokinetics and widely varying antibiotic exposures. The impact of altered pharmacokinetics on bacterial killing and resistance has not been characterized in the dynamic hollow-fibre in vitro infection model (HFIM).

Methods: A clinical Pseudomonas aeruginosa isolate (piperacillin MIC 4 mg/L) was studied in the HFIM (inoculum ∼10(7) cfu/mL).

Race/Ethnicity and Treatment Outcome in a Randomized Controlled Trial for Trichotillomania (Hair-Pulling Disorder).

Objective: Treatment outcome was compared among non-Hispanic White and racial/ethnic minority participants with trichotillomania (TTM), or hair-pulling disorder.

Method: Symptom severity, quality of life, and TTM-related disability were compared in a behavior therapy trial with a stepped care approach: web-based self-help and then individual behavior therapy. The sample comprised 72% (n = 38) non-Hispanic White participants and 28% (n = 15) minority participants.

Predictors of Relapse Following Treatment of Trichotillomania.

Objective: This study sought to identify predictors of relapse in a behavior therapy trial for trichotillomania (TTM), or hair-pulling disorder. Relapse is common after treatment for TTM, and only a few studies have examined what might predict relapse.

Method: Data was examined from a TTM treatment study with a stepped-care approach (step 1.

Validating indicators of treatment response: application to trichotillomania.

Different studies of the treatment of trichotillomania (TTM) have used varying standards to determine the proportion of patients who obtain clinically meaningful benefits, but there is little information on the similarity of results yielded by these methods or on their comparative validity. Data from a stepped-care (Step 1: Web-based self-help; Step 2: Individual behavior therapy; N = 60) treatment study of TTM were used to evaluate 7 potential standards: complete abstinence, ≥ 25% symptom reduction, recovery of normal functioning, and clinical significance (recovery + statistically reliable change), each of the last 3 being measured by self-report (Massachusetts General Hospital Hairpulling Scale; MGH-HPS) or interview (Psychiatric Institute Trichotillomania Scale). Depending on the metric, response rates ranged from 25 to 68%.

Stepped care in the treatment of trichotillomania.

Objective: There are effective treatments of trichotillomania (TTM), but access to expert providers is limited. This study tested a stepped care model aimed at improving access.

Method: Participants were 60 (95% women, 75% Caucasian, 2% Hispanic) adults (M = 33.

Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases.

Certain autoimmune diseases as well as asthma have increased in recent decades, particularly in developed countries. The hygiene hypothesis has been the prevailing model to account for this increase; however, epidemiology studies also support the contribution of diet and obesity to inflammatory diseases. Diet affects the composition of the gut microbiota, and recent studies have identified various molecules and mechanisms that connect diet, the gut microbiota, and immune responses.