Infections caused by antibiotic-resistant pathogens, particularly Gram-negative bacteria, have become increasingly challenging to successfully treat. The beta-lactam antibiotic subclass, the carbapenems, have proven valuable for the treatment of such Gram-negative bacterial infections due to their spectrum and β-lactamase stability properties. However, all marketed carbapenems to date are parenterally administered to adult patients. Areas covered: One carbapenem, tebipenem-pivoxil (TBPM-PI), is an oral prodrug that was approved in Japan for pediatric use only in 2009. This review summarizes preclinical and clinical data for TBPM-PI, which is now in clinical development again this time for use as the first oral carbapenem available for treatment of bacterial infections in adult patients. Expert commentary: There is an urgent unmet need with an increasing prevalence of fluoroquinolone-resistant and ESBL-producing Gram-negative pathogens in the hospital and community setting. Carbapenems have traditionally been considered the drugs of choice for infections caused by enterobacteria producing ESBL and AmpC enzymes because they are not affected by these resistance mechanisms. The carbapenem, TBPM-PI, offers an oral option, particularly as step-down therapy, for use of this class in the treatment of serious Gram-negative infections.

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr, formerly SPR994) is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) Gram-negative pathogens, including quinolone-resistant and extended-spectrum-β-lactamase-producing Enterobacteriaceae. The safety and pharmacokinetics (PK) of tebipenem were studied after administration of single and multiple ascending oral doses of TBPM-PI-HBr in fed and fasted states. Healthy adults received single oral doses of TBPM-PI-HBr at 100 mg to 900 mg or placebo (n = 108) or multiple doses of 300 mg or 600 mg every 8 h or placebo (n = 16) for 14 days. In the single-ascending-dose (SAD) phase, mean tebipenem plasma concentrations increased in a linear and dose proportional manner for doses of 100 to 900 mg and were comparable in the fasted and fed states for the 300- and 600-mg doses. In the MAD phase, tebipenem maximum concentration (Cmax) was reached within 1.5 h and was dose proportional on day 1 and higher than dose proportional (2.7-fold) on day 14. AUC was more than 2-fold greater on day 1 (2.7-fold) and day 14 (2.5-fold) for 600 mg q8h than for 300 mg q8h. Approximately 55% to 60% of tebipenem was recovered in the urine. TBPM-PI-HBr was well tolerated; mild, transient diarrhea was the most commonly reported adverse event. TBPM-PI-HBr provides an orally bioavailable carbapenem option to treat serious infections caused by MDR Enterobacteriaceae and has the potential to decrease the need for intravenous antibiotic therapy in the hospital or outpatient setting. (This study has been registered at ClinicalTrials.gov under identifier NCT03395249.)

Post transplantation constrictive bronchiolitis (PTCB) is the most common pulmonary complication among longterm survivors of allogeneic hematopoietic stem cell transplantation (HSCT). It is a late manifestation of GVHD. Its treatment with high-dose systemic corticosteroids and other immunosuppressive regimens is associated with multiple side effects. Topical corticosteroids are used for the treatment of other manifestations of GVHD to minimize these side effects. We conducted a retrospective analysis of a series of adult patients to evaluate the efficacy of high-dose inhaled corticosteroids in the treatment of PTCB. Seventeen patients with new-onset airflow obstruction were diagnosed with PTCB. Their forced expiratory volume in 1 s (FEV1) declined from a median of 84% (range, 56-119) before HSCT to 53% (26-82) after HSCT. All patients received inhaled fluticasone propionate 500-940 lg two times daily. Symptoms of airway obstruction improved and FEV1 stabilized 3-6 months after treatment. We conclude that high-dose inhaled corticosteroids may be effective in the treatment of PTCB and propose a plausible mechanism of its action. A prospective evaluation of its efficacy is warranted.

Nephropathy is a leading cause of morbidity and mortality and its prevalence is continuously increasing in industrialised nations. Nephropathy is characterised to varying degrees by nodular glomerulosclerosis, glomerular basement membrane thickness and mesangial expansion, leading to a decline in glomerular filtration rate, persistent elevated albuminuria, elevated arterial blood pressure and fluid retention. Hyperglycaemia, hyperlipidaemia and hypertension are considered to be the major risk factors implicated in the progression of nephropathy. Various signalling systems, such as vasoconstrictor peptides, inflammatory mediators, growth factors and adhesion molecules, are involved in the pathogenesis of nephropathy. At present, no promising therapy is available to treat patients with nephropathy due to lack of understanding of signalling culprits involved in the pathogenesis of nephropathy. Animal models are being developed to better understand the disease pathogenesis and develop drugs for nephropathy. In the present review, we have discussed various animal models for nephropathy, which may open vistas for developing new drugs to treat nephropathy.

DiabCare Bangladesh 2008 evaluated the current status of diabetes care in Bangladesh as a continuation of similar cross-sectional study conducted previously in 1998. The current study recruited 1952 patients from general hospitals, diabetes clinics and referral clinics to study current scenario of diabetes management from 01 March 2009 to 31 March 2009. We report the results of type 2 diabetic population who constituted 95.3% (n=1860). Results showed deteriorating glycaemic control with mean HbA1c of 8.6±2.0% with only 23.1% of the patients achieving American Diabetes Association (ADA) target of <7%. 896 (47.0%) patients were hypertensive and 850 (94.9%) were on antihypertensive medication. 70.8% of patients had LDL levels >2.6 mmol/L; 43.8% had triglycerides >2.2 mmol/L; 44.1% had HDL<1 mmol/L despite 48% of the patients being on lipid lowering agents. Microvascular, macrovascular and severe late complications were reported in 39.2%, 9.9% and 12.1% patients respectively. The rates of diabetic complications were cataract 12.9%, microalbuminuria 15.7%, neuropathy symptoms 31.7%, leg amputation 1.2% and history of angina pectoris was 6.6%. Quality of life evaluation showed that about half of patients have poor quality of life. Also, there was poor adherence to diet, exercise and self testing of blood glucose. In conclusion, majority of the patients were still not satisfactorily controlled. There is an urgent need for effective remedial measures to increase adherence to practice guidelines and to educate both patients and healthcare personnel on importance of achieving clinical targets for metabolic control.