Effect of tebipenem pivoxil hydrobromide on the normal gut microbiota of a healthy adult population in Sweden: a randomised controlled trial.

Background: Antimicrobials cause perturbations in the composition and diversity of the host microbiome. We aimed to compare gut microbiome perturbations caused by oral tebipenem pivoxil hydrobromide (a novel carbapenem) and by amoxicillin-clavulanic acid (an orally administered β-lactam-β-lactam inhibitor combination widely used in clinical practice).

Methods: We did a phase 1, single-centre, randomised, parallel-group, active-control trial to evaluate the effect of tebipenem pivoxil hydrobromide on the human gut microbiota.

Activity of Omadacycline and Five Comparators against Contemporary Ribotypes of Clostridioides difficile in Stockholm, Sweden.

Clostridioides difficile infection represents a growing clinical challenge. The new compound omadacycline is a potential treatment alternative, as many antibiotics have limited activity or are rarely used due to costs and side effects. The activity of omadacycline and five comparators was assessed with agar dilution on a 2015-to-2018 collection of 65 C.

In vitro activity of ceftazidime-avibactam against Gram-negative isolates collected in 18 European countries, 2015-2017.

Background: Between 2015-2017, 21 850 Enterobacterales isolates and 6156 Pseudomonas aeruginosa (P. aeruginosa) isolates were collected by 77 centers in 18 European countries as part of the International Network for Optimal Resistance Monitoring (INFORM) study (which was included into the Antimicrobial Testing Leadership and Surveillance [ATLAS] study in 2018).

Methods: A central reference laboratory performed antimicrobial susceptibility testing using broth microdilution panels according to Clinical and Laboratory Standards Institute guidelines.

Clostridium difficile Infection-Daily Symptoms (CDI-DaySyms™) questionnaire: psychometric characteristics and responder thresholds.

Background: The purpose of the current study was to determine the final content validation, psychometric characteristics, clinically meaningful improvement, and responder thresholds of the Clostridium difficile infection (CDI)-Daily Symptoms (CDI-DaySyms™) patient-reported outcome (PRO) questionnaire.

Methods: This validation study was part of two phase III studies (NCT01987895 and NCT01983683) conducted in patients with mild-to-moderate or severe CDI who completed the CDI-DaySyms™ daily throughout the treatment period. The questionnaire was evaluated in three stages: final PRO item content validation (Stage I); psychometric evaluation of reliability and construct validity (Stage II); and determination of clinically meaningful improvement and responder thresholds using distribution-based methods (Stage III).

Cadazolid for the treatment of Clostridium difficile infection: results of two double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials.

Background: Cadazolid is a novel quinoxolidinone antibiotic developed for treating Clostridium difficile infection. We aimed to investigate the safety and efficacy of cadazolid compared with vancomycin in patients with C difficile infection.

Methods: IMPACT 1 and IMPACT 2 were identically designed, multicentre, double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials.

The CDI-DaySyms: Content Development of a New Patient-Reported Outcome Questionnaire for Symptoms of Clostridium difficile Infection.

Objectives: To develop a patient-reported outcome (PRO) questionnaire for symptoms of Clostridium difficile infection (CDI) following the US Food and Drug Administration PRO guidelines.

Methods: Patients' experiences of CDI symptoms were elicited in open-ended discussions with patients and nurses at five US sites (stage 1). A draft PRO measure was developed after demonstration of concept saturation.

In-vitro activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota.

Solithromycin is a novel fluoroketolide with high activity against bacteria associated with community-acquired respiratory tract infections as well as gonorrhea. However, data on the activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota are scarce. In this study, 1024 Gram-positive and Gram-negative anaerobic isolates from the normal intestinal microbiota were analyzed for in-vitro susceptibility against solithromycin and compared to azithromycin, amoxicillin/clavulanic acid, ceftriaxone, metronidazole and levofloxacin by determining the minimum inhibitory concentration (MIC).

Methicillin-resistant Staphylococcus aureus in Stockholm, Sweden: Molecular epidemiology and antimicrobial susceptibilities to ceftaroline, linezolid, mupirocin and vancomycin in 2014.

Methicillin-resistant Staphylococcus aureus (MRSA) is a public health problem worldwide. The aim of the present study was to investigate the molecular epidemiology and antimicrobial susceptibilities of MRSA strains in Stockholm, Sweden in 2014. Pulsed-field gel electrophoresis (PFGE) was used to characterise the strains.

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance.

Ecological Effect of Solithromycin on Normal Human Oropharyngeal and Intestinal Microbiota.

Solithromycin is a new fluoroketolide. The purpose of the present study was to investigate the effect of orally administered solithromycin on the human oropharyngeal and intestinal microbiota. Thirteen healthy volunteers (median age, 27.

Clostridium difficile recurrences in Stockholm.

Sixty-eight hospital-admitted patients with a first episode of Clostridium difficile infection (CDI) were included and followed up during 1 year. Faeces samples were collected at 1, 2, 6 and 12 months after inclusion and analyzed for the presence of C. difficile toxin B, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR.

Molecular characteristics of Clostridium difficile strains from patients with a first recurrence more than 8 weeks after the primary infection.

Background/purpose: Nearly all published studies of recurrent Clostridium difficile infections (CDI) report recurrent CDI within 8 weeks after the primary infection. This study explored the molecular characteristics of C. difficile isolates from the first recurrent CDI more than 8 weeks after the primary infection.

Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces.

Unlabelled: Due to the spread of resistance, antibiotic exposure receives increasing attention. Ecological consequences for the different niches of individual microbiomes are, however, largely ignored. Here, we report the effects of widely used antibiotics (clindamycin, ciprofloxacin, amoxicillin, and minocycline) with different modes of action on the ecology of both the gut and the oral microbiomes in 66 healthy adults from the United Kingdom and Sweden in a two-center randomized placebo-controlled clinical trial.

WSES guidelines for management of Clostridium difficile infection in surgical patients.

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent.

Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection.

Cadazolid, a novel fluoroquinolone-oxazolidinone antibiotic, exhibits potent in vitro activity against Clostridium difficile, including the epidemic BI/NAP1/027 strain. This multicenter, randomized, double-blind, active reference group, phase 2 study evaluated the efficacy and safety of oral cadazolid in treatment of adult patients with C. difficile infection (CDI).

Ecological Effect of Ceftaroline-Avibactam on the Normal Human Intestinal Microbiota.

Ceftaroline-avibactam is a new combination of the antibiotic ceftaroline with a novel non-β-lactam β-lactamase inhibitor, avibactam. The purpose of the present study was to investigate the effect of ceftaroline-avibactam on the human intestinal microbiota. Fourteen healthy volunteers received ceftaroline-avibactam (600 mg ceftaroline fosamil and 600 mg avibactam) intravenously over 2 h every 8 h on days 1 to 6 and as a single dose on day 7.

Impact of Ciprofloxacin and Clindamycin Administration on Gram-Negative Bacteria Isolated from Healthy Volunteers and Characterization of the Resistance Genes They Harbor.

The aim of this study was to assess the impact of ciprofloxacin, clindamycin, and placebo administration on culturable Gram-negative isolates and the antibiotic resistance genes they harbor. Saliva and fecal samples were collected from healthy human volunteers before and at intervals, up to 1 year after antibiotic administration. Samples were plated on selective and nonselective media to monitor changes in different colony types or bacterial species.

Ecological effect of ceftazidime/avibactam on the normal human intestinal microbiota.

Ceftazidime/avibactam is a new combination of the antibiotic ceftazidime with the novel, non-β-lactam β-lactamase inhibitor avibactam. The purpose of the present study was to investigate the effect of ceftazidime/avibactam on the human intestinal microbiota following intravenous (i.v.

Determining the Long-term Effect of Antibiotic Administration on the Human Normal Intestinal Microbiota Using Culture and Pyrosequencing Methods.

The purpose of the study was to assess the effect of ciprofloxacin (500 mg twice daily for 10 days) or clindamycin (150 mg 4 times daily for 10 days) on the fecal microbiota of healthy humans for a period of 1 year as compared to placebo. Two different methods, culture and microbiome analysis, were used. Fecal samples were collected for analyses at 6 time-points.

Development of antimicrobial resistance in the normal anaerobic microbiota during one year after administration of clindamycin or ciprofloxacin.

Thirty healthy subjects (15 males and 15 females) were randomly assigned in three groups and clindamycin (150 mg qid) or ciprofloxacin (500 mg bid) or placebo was given for a 10-day period. Skin, nasal, saliva, faeces samples were collected at day - 1, day 11, 1 month, 2 months, 4 months and 12 months post administration for microbiological analysis. Ciprofloxacin or clindamycin had no impact on the anaerobic skin microbiota and the proportions of antibiotic resistant anaerobic bacteria were similar as in the placebo group.

Risk factors of Clostridium difficile infections among patients in a university hospital in Shanghai, China.

Clostridium difficile infection (CDI) is an increasing concern in China. However, the risk factors of CDI are rarely reported in the Chinese population. A prospective observational study was therefore conducted among patients with hospital-acquired C.

In vitro activity of MCB3681 against Clostridium difficile strains.

One hundred fourteen Clostridium difficile strains were collected from 67 patients and analyzed for the presence of C. difficile toxin B by the cell cytotoxoicity neutralization assay, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR. All strains were also PCR-ribotyped.

Ecological impact of MCB3837 on the normal human microbiota.

MCB3837 is a novel, water-soluble, injectable prodrug that is rapidly converted to the active substance MCB3681 in vivo following intravenous (i.v.) administration.

Alternative strategies for proof-of-principle studies of antibacterial agents.

The proof that a new antibacterial agent is not only active in vitro but also effective in vivo under clinically relevant conditions is currently provided (i) by using appropriate nonclinical models of infection and pharmacokinetic-pharmacodynamic (PK-PD) analysis providing evidence of the likelihood of clinical efficacy and (ii) by examining the study drug in exploratory clinical trials, as well as dose and schedule finding during phase II of clinical development. This approach is both time-consuming and costly. Furthermore, PK-PD targets for any novel antibacterial agent cannot be derived from studies with experimental animals.