Patient outcomes by baseline pathogen resistance phenotype and genotype in CERTAIN-1, a Phase 3 study of cefepime-taniborbactam versus meropenem in adults with complicated urinary tract infection.

Unlabelled: CERTAIN-1 was a Phase 3, double-blind, randomized, parallel group study of the efficacy and safety of cefepime-taniborbactam versus meropenem in the treatment of adults with complicated urinary tract infection (cUTI), including acute pyelonephritis. We determined susceptibility of Enterobacterales and baseline pathogens to cefepime-taniborbactam and comparators and characterized β-lactam resistance mechanisms. Microbiologic response and clinical response were assessed in patient subsets defined by baseline pathogens that were of cefepime-, multidrug-, or carbapenem-resistant phenotype or that carried β-lactamase genes.

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.

Cefepime-Taniborbactam in Complicated Urinary Tract Infection.

Background: Carbapenem-resistant Enterobacterales species and multidrug-resistant are global health threats. Cefepime-taniborbactam is an investigational β-lactam and β-lactamase inhibitor combination with activity against Enterobacterales species and expressing serine and metallo-β-lactamases.

Methods: In this phase 3, double-blind, randomized trial, we assigned hospitalized adults with complicated urinary tract infection (UTI), including acute pyelonephritis, in a 2:1 ratio to receive intravenous cefepime-taniborbactam (2.

Effect of an Antacid (Aluminum Hydroxide/Magnesium Hydroxide/Simethicone) or a Proton Pump Inhibitor (Omeprazole) on the Pharmacokinetics of Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) in Healthy Adult Subjects.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is a novel oral carbapenem prodrug being developed for the treatment of serious bacterial infections. This open-label, 3-period, fixed sequence study evaluated the effect of gastric acid-reducing agents, aluminum hydroxide/magnesium hydroxide/simethicone, and omeprazole on the pharmacokinetics (PK) of tebipenem (TBP), the active moiety, following coadministration with immediate release TBP-PI-HBr during fasting. In Period 1, subjects received a single oral dose of TBP-PI-HBr 600 mg (2 × 300 mg tablets).

Pharmacokinetics of Oral Tebipenem Pivoxil Hydrobromide in Subjects with Various Degrees of Renal Impairment.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral carbapenem prodrug antimicrobial agent with broad-spectrum activity that includes multidrug-resistant (MDR) . This study evaluated the safety, tolerability, and pharmacokinetics of TBP-PI-HBr in healthy subjects with normal renal function (cohort 1) and subjects with various degrees of renal impairment (RI [cohorts 2 to 4]) or end-stage renal disease (ESRD) receiving hemodialysis (HD) (cohort 5). Subjects in cohorts 1 to 4 received a single oral dose of TBP-PI-HBr (600 mg).

Bioequivalence of two oral formulations of tebipenem pivoxil hydrobromide in healthy subjects.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is a novel oral carbapenem prodrug of tebipenem (TBP), the active moiety, currently in development for treating serious bacterial infections. This study assessed the bioequivalence (BE) of the clinical trial and registration tablet formulations of TBP-PI-HBr and evaluated the effect of food on the pharmacokinetics (PKs) of tebipenem. This was a single center, open-label, randomized, single-dose, three-sequence, four-period crossover, BE, and food-effect study.

Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial.

Importance: New antibacterials are needed to treat community-acquired bacterial pneumonia (CABP) because of growing antibacterial resistance and safety concerns with standard care.

Objective: To evaluate the efficacy and adverse events of a 5-day oral lefamulin regimen in patients with CABP.

Design, Setting, And Participants: A phase 3, noninferiority randomized clinical trial conducted at 99 sites in 19 countries that included adults aged 18 years or older with a Pneumonia Outcomes Research Team (PORT) risk class of II, III, or IV; radiographically documented pneumonia; acute illness; 3 or more CABP symptoms; and 2 or more vital sign abnormalities.

Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial.

Background: Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP.

Methods: In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin at 150 mg intravenously (IV) every 12 hours or moxifloxacin at 400 mg IV every 24 hours.

Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme.

Objectives: This analysis evaluated the clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa isolates pooled from the adult Phase III clinical trials in patients with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI) or nosocomial pneumonia (NP) including ventilator-associated pneumonia (VAP).

Methods: Baseline isolates from five Phase III randomized controlled trials of ceftazidime/avibactam versus predominantly carbapenem comparators in patients with cIAI (RECLAIM 1 and 2; NCT01499290 and RECLAIM 3; NCT01726023), cUTI (RECAPTURE 1 and 2; NCT01595438 and NCT01599806), NP including VAP (REPROVE; NCT01808092) and cIAI or cUTI caused by ceftazidime-non-susceptible Gram-negative pathogens (REPRISE; NCT01644643) were tested for MDR status and susceptibility to ceftazidime/avibactam and carbapenem-based comparators using CLSI broth microdilution methodology. Microbiological and clinical responses for patients with ≥1 MDR Enterobacteriaceae or P.

Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program.

Background: The global emergence of carbapenem-resistant Enterobacteriaceae highlights the urgent need to reduce carbapenem dependence. The phase 3 RECAPTURE program compared the efficacy and safety of ceftazidime-avibactam and doripenem in patients with complicated urinary tract infection (cUTI), including acute pyelonephritis.

Methods: Hospitalized adults with suspected or microbiologically confirmed cUTI/acute pyelonephritis were randomized 1:1 to ceftazidime-avibactam 2000 mg/500 mg every 8 hours or doripenem 500 mg every 8 hours (doses adjusted for renal function), with possible oral antibiotic switch after ≥5 days (total treatment duration up to 10 days or 14 days for patients with bacteremia).

Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study.

Background: Carbapenems are frequently the last line of defence in serious infections due to multidrug-resistant Gram-negative bacteria, but their use is threatened by the growing prevalence of carbapenemase-producing pathogens. Ceftazidime-avibactam is a potential new agent for use in such infections. We aimed to assess the efficacy, safety, and tolerability of ceftazidime-avibactam compared with best available therapy in patients with complicated urinary tract infection or complicated intra-abdominal infection due to ceftazidime-resistant Gram-negative pathogens.

Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program.

Background: When combined with ceftazidime, the novel non-β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239).

Methods: The primary end point was clinical cure at test-of-cure visit 28-35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance).

β-Lactamase Characterization of Gram-Negative Pathogens Recovered from Patients Enrolled in the Phase 2 Trials for Ceftazidime-Avibactam: Clinical Efficacies Analyzed against Subsets of Molecularly Characterized Isolates.

The correlation of the clinical efficacies of ceftazidime-avibactam and comparators (carbapenems) was evaluated against baseline Gram-negative isolates having characterized β-lactam resistance mechanisms from complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) phase 2 trials. Enterobacteriaceae displaying ceftriaxone and/or ceftazidime MICs of ≥ 2 μg/ml (69 isolates) and nonfermentative Gram-negative bacilli (NF-GNB [three isolates]) with ceftazidime MICs of ≥ 16 μg/ml were characterized for their narrow- and extended-spectrum β-lactamase (ESBL) content. Enterobacteriaceae (one isolate) and NF-GNB (three isolates) with imipenem/meropenem MICs of ≥ 2 and ≥ 16 μg/ml, respectively, were tested for carbapenemases.

Genetic variants and susceptibility to neurological complications following West Nile virus infection.

To determine genetic factors predisposing to neurological complications following West Nile virus infection, we analyzed a cohort of 560 neuroinvasive case patients and 950 control patients for 13 371 mostly nonsynonymous single-nucleotide polymorphisms (SNPs). The top 3 SNPs on the basis of statistical significance were also in genes of biological plausibility: rs2066786 in RFC1 (replication factor C1) (P = 1.88 × 10(-5); odds ratio [OR], 0.

Impact of antimicrobial stewardship programme changes on unnecessary double anaerobic coverage therapy.

Background: Concern has been raised over the practice of unnecessary double anaerobic coverage therapy (DACT) in the hospital setting. However, the incidence of and risk factors for unnecessary DACT are not well studied. On 8 September 2008, the antimicrobial stewardship programme (ASP) at our institution was modified such that several antibiotics, including ampicillin/sulbactam and metronidazole, no longer required pre-approval.

Decreased post-transplant survival among heart transplant recipients with pre-transplant hepatitis C virus positivity.

Background: Transplant centers are reluctant to perform heart transplantation in patients with hepatitis C virus (HCV) infection because augmented immunosuppression could potentially increase mortality. However, there have been few studies examining whether HCV infection reduces survival after heart transplantation.

Methods: We used data from the the U.

Child care center exclusion policies and directors' opinions on the use of antibiotics.

We studied exclusion policies and child care center directors' opinions regarding antibiotic use for childhood illnesses. Among 135 respondents, 96.9% reported that they had written policies on exclusion of children for acute illnesses.

Risk factors and clinical impact of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae.

Background: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae is an emerging pathogen with serious clinical and infection control implications. To our knowledge, no study has specifically examined risk factors for KPC-producing K.

Increased incidence of cytomegalovirus infection in high-risk liver transplant recipients receiving valganciclovir prophylaxis versus ganciclovir prophylaxis.

Optimal measures for the prevention of cytomegalovirus (CMV) in high-risk orthotopic liver transplant (OLT) patients are unknown. The charts of high-risk OLT recipients with 12 months of follow-up who were transplanted over a 44-month period were reviewed. The incidence of CMV disease in CMV-seropositive donor/CMV-seronegative recipient patients receiving valganciclovir or ganciclovir prophylaxis was compared.

Isolation precautions for antibiotic-resistant bacteria in healthcare settings.

Purpose Of Review: Emergence of drug-resistant bacteria and new or changing infectious pathogens is an important public health problem. Transmission of these pathogens in an acute care setting may occur frequently if proper precautions are not taken. Despite several guidelines and an abundance of literature on the prevention of transmission of epidemiologically important organisms in the healthcare setting, substantial controversy exists.

Stockpiling drugs for an avian influenza outbreak: examining the surge in oseltamivir prescriptions during heightened media coverage of the potential for a worldwide pandemic.

Objective: During fall 2005, personal stockpiling of oseltamivir for use during an outbreak of H5N1 influenza virus infection was widely reported. The present study aimed to identify indications for oseltamivir prescriptions to determine whether oseltamivir that was not intended for seasonal influenza was inappropriately consumed and to compare persons who were likely to have stockpiled oseltamivir and those who did not with respect to their knowledge, understanding, concerns, and expectations regarding avian influenza.

Design: Survey to evaluate usage patterns for oseltamivir and assess views about avian influenza.

Coadministration of oral levofloxacin with agents that impair absorption: impact on antibiotic resistance.

Coadministration of oral divalent or trivalent cation-containing compounds with oral fluoroquinolones may impair fluoroquinolone absorption. Among 3,134 patients who received a course of oral levofloxacin, coadministration was significantly associated with subsequent identification of a levofloxacin-resistant isolate. Strategies to curb the emergence of fluoroquinolone resistance should include avoiding the coadministration of divalent or trivalent cation-containing compounds and fluoroquinolone.