HDLS cases have been located in Germany, Norway, Sweden, and the United States, showing an international distribution focusing between Northern Europe and the United States.Through the study of numerous kindred, it was found that the disease did not occur among just males or females, but rather was evenly distributed indicative of an autosomal rather than a sex-linked genetic disorder. It was also observed that the HDLS cases did not skip generations as it would occur with a recessive inheritance, and as such has been labeled autosomal dominant. History
This disease was first described in 1984 by Axelsson et al. in a large Swedish pedigree. It is a disorder better known to neuropathologists than clinicians. A neuropathologist with an interest in HDLS, Dr. Dennis W. Dickson, has identified a number of cases from neuropathology study of brains submitted for investigation of familial adult-onset dementia and movement disorders in New York and later in Florida. Recognition of the importance of this disorder as a cause of adult onset dementia and movement disorders was further heightened in 1997 at the Mayo Clinic when Dr. Zbigniew K. Wszolek identified a family with HDLS that was initially thought to be due to another disease process (FTDP-17), but only an autopsy of one and then other family members revealed it to be HDLS. Wszolek established an international consortium in 2005 to identify other families and to collect DNA or brain samples from family members for neuropathologic confirmation and genetic research at the Mayo Clinic in Florida.
It has no useful activity against Gram-positive bacteria or anaerobes. It is known to be effective against a wide range of bacteria including Citrobacter, Enterobacter, E. coli, Haemophilus, Klebsiella, Proteus, and Serratia species. The following represents minimum inhibitory concentration (MIC) susceptibility data for a few medically significant microorganisms. Staphylococcus aureus 8 - >128 μg/ml
Staphylococcus epidermidis 8 - 32 μg/ml
Streptococcus pyogenes 8 - ≥128 μg/mlSynergism between aztreonam and arbekacin or tobramycin against P. aeruginosa has been suggested. Spectrum of activity
Acinetobacter anitratus, Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis are generally susceptible to aztreonam, while some staphylococci, Staphylococcus aureus, Staphylococcus haemolyticus and Xanthomonas maltophilia are resistant to it. Furthermore, Aeromonas hydrophila, Citrobacter koseri (Citrobacter diversus), Pantoea agglomerans (Enterobacter agglomerans), Haemophilus spp. and Streptococcus pyogenes have developed resistance to aztreonam to varying degrees.Aztreonam can be safely used in patients with a penicillin or cephalosporin allergy (except for patients with a ceftazidime allergy as ceftazidime and aztreonam share a similar side chain). It is also frequently used as an alternative to aminoglycosides because is not ototoxic or nephrotoxic.Aztreonam use has been recently reconsidered for human infections sustained by metallo-beta-lactamase (MBL)-producing Gram-negative bacteria. In these circumstances aztreonam is combined with avibactam (ceftazidime/avibactam). The combination of aztreonam and avibactam has demonstrated to be active against 80% of MBL isolates reaching a clinical infection resolution in 80% of MBL-infected patients. Administration
Aztreonam is poorly absorbed when given orally, so it must be administered as an intravenous or intramuscular injection (trade name Azactam), or inhaled (trade name Cayston) using an ultrasonic nebulizer.