In cases where osteopenia progresses with age, bone mineral density in the ribs is typically more severe than in the vertebrae. In some cases bone mineral density T-score will drop below -2.5, indicating osteoporosis. There is some evidence that osteopenia may be connected with associated kidney abnormalities in GSD I, particularly glomular hyperfiltration. The condition also seems responsive to calcium supplementation. In many cases bone mineral density can increase and return to the normal range given proper metabolic control and calcium supplementation alone, reversing osteopenia. Kidney effects
The kidneys are usually 10 to 20% enlarged with stored glycogen. In adults with GSD I, chronic glomerular damage similar to diabetic nephropathy may lead to kidney failure. GSD I may present with various kidney complications. Renal tubular abnormalities related to hyperlactatemia are seen early in life, likely because prolonged lactic acidosis is more likely to occur in childhood. This will often present as Fanconi syndrome with multiple derangements of renal tubular reabsorption, including tubular acidosis with bicarbonate and phosphate wasting. These tubular abnormalities in GSD I are typically detected and monitored by urinary calcium. Long term these derangements can exacerbate uric acid nephropathy, otherwise driven by hyperlactatemia. In adolescence and beyond, glomerular disease may independently develop, initially presenting as glomerular hyperfiltration indicated by elevated urinary eGFR. Splenomegaly
Enlargement of the spleen (splenomegaly) is common in GSD I and has two primary causes.
These include Haemophilus, Moraxella and Neisseria pathogens, and infections caused by Acinectobacter baumannii.The antibacterial spectrum of ceftazidime/avibactam includes nearly all Enterobacteriaceae, including ceftazidime-resistant strains. The activity of ceftazidime/avibactam against the important hospital pathogen Pseudomonas aeruginosa is variable, due to the potential presence of other resistance mechanisms in addition to β-lactamase production. Synergy was observed for avibactam with ceftazidime in the Burkholderia cepacia complex. Adverse events
When used to treat life-threatening infections, ceftazidime/avibactam is more likely than carbapenem antibiotics to cause serious adverse events, including worsening kidney function and gastrointestinal adverse effects. Mechanism of action
Bacterial resistance to cephalosporins is often due to bacterial production of β-lactamase enzymes that deactivate these antibiotics. Avibactam inhibits some (but not all) bacterial β-lactamases. Also, some bacteria are resistant to cephalosporins by other mechanisms, and therefore avibactam doesnt work. Avibactam is not active against New Delhi metallo-β-lactamase 1 (NDM-1). Avibactam inhibits Klebsiella pneumoniae carbapenemases (KPCs), and AmpC-type β-lactamases, which are resistant to the other clinically-available β-lactamases, tazobactam and clavulanic acid. Regulatory
It was granted approval for marketing in the United States by the Food and Drug Administration (FDA) in February 2015. It was granted approval for marketing in Europe by the European Medicines Agency in 2016. During its clinical development, ceftazidime/avibactam was designated as a Qualified Infectious Disease Product under the Generating Antibiotic Incentives Now provision of the Food and Drug Administration Safety and Innovation Act. Development of ceftazidime/avibactam was fast-tracked by the FDA due to the shortage of drugs for treatment of infections due to antibiotic-resistant bacteria. References
External links
"Avibactam mixture with ceftazidime".