Evaluation of Factors Predictive of Efficacy Among Patients With Complicated Urinary Tract Infection and/or Acute Pyelonephritis.

Background: Antibiotic treatment for complicated urinary tract infections (cUTI)/acute pyelonephritis (AP) is often followed by recurrent bacteriuria in the absence of clinical symptoms. To understand factors predictive of clinical and microbiologic outcomes in patients with cUTI/AP, multivariable analyses were undertaken using pooled data from a global, phase 3 cUTI study.

Methods: Using data from 366 tebipenem pivoxil hydrobromide- and 378 ertapenem-treated patients from the Study to Assess the Efficacy, Safety and Pharmacokinetics of Orally Administered Tebipenem Pivoxil Hydrobromide (SPR994) Compared to Intravenous Ertapenem in Participants With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) infected with Enterobacterales uropathogens, multivariable analyses for dichotomous efficacy endpoints were performed using logistic regression and pharmacokinetic-pharmacodynamic relationships were evaluated.

Impact of antibiotic pharmacokinetics in urine on recurrent bacteriuria following treatment of complicated urinary tract infections.

The clinical relevance of bacteriuria following antibiotic treatment of complicated urinary tract infections in clinical trials remains controversial. We evaluated the impact of urine pharmacokinetics on the timing of recurrent bacteriuria in a recently completed trial that compared oral tebipenem pivoxil hydrobromide to intravenous ertapenem. The urinary clearance and urine dwell time of ertapenem were prolonged relative to tebipenem and were associated with a temporal difference in the repopulation of bladder urine with bacteria following treatment, potentially confounding the assessment of efficacy.

Absorption, Metabolism, and Excretion of [C]-Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) in Healthy Male Subjects.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral prodrug of pharmacologically active moiety tebipenem (TBP), which is a carbapenem with activity against multidrug-resistant Gram-negative pathogens. Conversion from the prodrug to the active moiety, namely, TBP, occurs in the enterocytes of the gastrointestinal tract via intestinal esterases. The absorption, metabolism, and excretion in humans were evaluated, following the administration of a single oral dose of [C]-TBP-PI-HBr.

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.

First-in-Human Evaluation of the Safety, Tolerability, and Pharmacokinetics of SPR720, a Novel Oral Bacterial DNA Gyrase (GyrB) Inhibitor for Mycobacterial Infections.

SPR720 (phosphate prodrug of SPR719) is a novel aminobenzimidazole bacterial DNA gyrase (GyrB) inhibitor in development for nontuberculous mycobacterial pulmonary disease (NTM-PD) and pulmonary tuberculosis. SPR719 has demonstrated activity against clinically relevant mycobacteria and in murine and hollow-fiber infection models. This phase 1 randomized, double-blind, placebo-controlled, single ascending dose (SAD)/multiple ascending dose (MAD) trial evaluated the safety, tolerability, and pharmacokinetics of SPR720/SPR719.

Single- and Multiple-Ascending-Dose Study of the Safety, Tolerability, and Pharmacokinetics of the Polymyxin Derivative SPR206.

Carbapenem-resistant Acinetobacter baumannii and are identified as urgent threats, and multidrug-resistant (MDR) Pseudomonas aeruginosa and extended-spectrum beta-lactamase (ESBL)-producing pathogens are identified as serious threats by the Centers for Disease Control and Prevention (CDC). SPR206 is a novel polymyxin derivative with potent and activity against A. baumannii, P.

Randomized, Double-Blind, Placebo- and Positive-Controlled Crossover Study of the Effects of Tebipenem Pivoxil Hydrobromide on QT/QTc Intervals in Healthy Subjects.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an orally available prodrug of tebipenem (TBP), a carbapenem with activity against multidrug-resistant Gram-negative pathogens. This study evaluated the effects of single therapeutic and supratherapeutic doses of TBP-PI-HBr on the heart rate-corrected QT interval (QTc) by assessing the concentration-QT interval relationship using exposure-response modeling. This was a randomized, double-blind, placebo- and active-controlled, single-dose, four-way crossover study.

Septic shock due to tuberculosis in Down syndrome.

Both Immune dysfunction and deficiency, are known in Down syndrome. Tuberculosis commonly presents as insidious illness and septicemic shock is its rare presentation, mostly in immunocompromized patients. We report a 16 year old boy with Down syndrome presenting with septicemic shock due to tuberculosis.

Randomized controlled trial of interrupted versus continuous sedative infusions in ventilated children.

Objective: To compare daily interruption vs. continuous sedative infusions in mechanically ventilated children with respect to lengths of mechanical ventilation and intensive care unit stay.

Design: Prospective randomized controlled trial.

A simple algorithm to eliminate ambiguities in EBSD orientation map visualization and analyses: application to fatigue crack-tips/wakes in aluminum alloys.

A simple algorithm is developed and implemented to eliminate ambiguities, in both statistical analyses of orientation data (e.g., orientation averaging) and electron backscattered diffraction (EBSD) orientation map visualization, caused by symmetrically equivalent orientations and the wrap-around or umklapp effect.

Need for harmonization of labeling of medical devices: a review.

Medical device labeling is any information associated with a device targeted to the patient or lay caregiver. It is intended to help assure that the device is used safely and effectively. Medical device labeling is supplied in many formats, for example, as patient brochures, patient leaflets, user manuals, and videotapes.

Isolated ptosis as acute ophthalmoplegia without ataxia, positive for anti-GQ1b immunoglobulin G.

Anti-GQ1b IgG antibody syndrome comprises a wide range of diseases presenting with ophthalmoplegia and ataxia. Anti-GQ1b antibodies have been strongly associated in the literature with Miller Fisher Syndrome, with acute ophthalmoplegia associated with Guillain-Barré syndrome, and with isolated ophthalmoplegia. Acute ophthalmoplegia presents as various combinations of external and internal ophthalmoplegia.

Ectrodactyly/split hand feet malformation.

Split-hand/split-foot malformation is a rare limb malformation with median clefts of the hands and feet and aplasia/hypoplasia of the phalanges, metacarpals and metatarsals. When present as an isolated anomaly, it is usually inherited as an autosomal dominant form. We report a case of autosomal recessive inheritance and discuss the antenatal diagnosis, genetic counseling and treatment for the malformation.