Massive presence of off-label medicines in Danish neonatal departments: A nationwide survey using national hospital purchase data.

There is currently insufficient knowledge of gestational age dependent medicine disposition in neonates. Accordingly, the use of off-label medication, i.e., use of medicines outside its approved marketing authorization, is high in the neonatal departments. By using data from the Danish National Pharmaceutical Hospital Purchase Database, we identified the most commonly occurring medications and calculated the on/off-label ratios for premature and term neonates. Data was extracted on ATC level 5 and based on defined daily doses as per WHO. Data covered the 4 high-level NICUs and 10 of 13 of the intermediate/standard level Danish neonatal departments. Of the identified medication, 87% and 70% did not have approved marketing authorization for use in premature and full-term neonates, respectively. Furthermore, one-fifth of the top 100 medicines did not have a (Danish) marketing license. Overall, off-label medication was widespread covering virtually all ATC groups and no ATC group had an off-label level lower than 50% (range 50%-100%). Finally, in 21% of medications, additives from 8 different chemical groups with potential deleterious effects for neonates were identified. In conclusion, off-label medication in the Danish neonatal departments is widespread. The pharmaceutical industry is unlikely to solve this problem, and we may for a very long time be occasionally forced to use off-label medication. Practical solution must therefore come from multidisciplinary clinical and academic collaboration. Use of formulation list as guidance for prescriptions and NICU-friendly galenic formulations may mitigate the problem temporarily while waiting for definitive studies.

Leclercia adecarboxylata: a case report and literature review of 74 cases demonstrating its pathogenicity in immunocompromised patients.

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the family Enterobacteriaceae. It has been described as an emerging human pathogen with the potential to cause severe infection in immunocompromised patients. The aim of this study was to describe a clinical case of infection with L. adecarboxylata and give a review of previous reports on infection. We report the presence of L. adecarboxylata in a patient initially admitted to our hospital for a lung transplant. She had diarrhoea, urinary tract infection and pneumonia caused by L. adecarboxylata. The isolate was resistant to trimethoprim-sulfamethoxazole and susceptible to 15 other antibiotics tested. The literature search for previous reports of infection with L. adecarboxylata resulted in 61 publications describing 74 cases. Bacteremia and wound infections were most often described, and only a few cases were fatal. L. adecarboxylata was most often found as a monomicrobial infection in immunocompromised patients, and as part of a polymicrobial infection in immunocompetent patients. The previously described isolates showed a high susceptibility to antibiotics, and treatment was efficient in most cases. Due to similarities in metabolic products, L. adecarboxylata might have been mistaken as Escherichia spp., but with new identification methods such as MALDI-TOF MS, it is possible to obtain a certain identification.