UTIs are one of the most important hospital-acquired infections in ICUs and are responsible for a large proportion of antibiotics prescribed. Few of the known risk factors are preventable, making it important to improve our understanding of the underlying causes of UTIs. In our study we have demonstrated that urine of severe trauma patients favours the growth of E. coli, which is the most frequently isolated species in UTIs [7, 25]. This effect is present during the first 24 hours, and remains at least until the fifth day after occurrence of trauma.
The changes in urinary composition induced not only by shock and trauma, but also by the urinary catheter could facilitate bacterial growth of both susceptible and resistant strains. Comparing the urine from trauma patients with that from healthy volunteers highlights a significant increase in glycosuria, urinary amino acids, urinary iron and norepinephrine concentrations, and a significant decrease in urinary urea concentrations and osmotic pressure. These could, together, play a role in the difference seen in bacterial growth. When norepinephrine was added to HV urine this alone did not facilitate bacterial growth.
Critically ill patients are often characterized by insulin resistance associated with impaired glucose tolerance and hyperglycemia. This stress induced-hyperglycemia leads to glycosuria, which is known to support bacterial growth in urine [26, 27].
The changes in urinary amino acids concentration that we have shown are also well known to influence growth of E. coli in urine [9, 11, 28]. Bacterial growth in urine is dependent on the availability of nitrogen. Some amino acids, such as serine or glutamic acid, increase E. coli growth [29, 30] (personal data). In critically ill patients, anabolic resistance and increased energy requirements lead to proteolysis, with a corresponding increase in the efflux of amino acids. Systemic inflammation alters amino acid transport through muscle cells. The increase in plasma amino acids levels could lead to a rise in urinary excretion [31–33]. In agreement with the work of Freund et al., we found that sulphur- containing amino acid (methionine), aromatic amino acids (phenylalanine and tyrosine) and branched chain amino acids (leucine and valine) are excreted early . Then, at the fifth day we showed an increase in the levels of excretion of the majority of amino acids as the result of catabolism, as well as renal damage in some cases. The urine iron level in healthy individuals is usually too low to support bacterial growth . The occurrence of phenomena such as rhabdomyolysis, blood transfusion or urinary tract trauma and also urinary catheter insertion could explain the higher iron levels. In our study, more than 80% of trauma patients had rhabdomyolysis, which leads to leakage of muscle proteins containing ferrous iron . Half of the patients were transfused during the first five days of their hospitalization, usually on the first day, with a mean of 3.4 units per patient. Blood transfusion can lead to intravascular haemolysis and haemoglobinuria. The role of iron in stimulating bacterial growth is confirmed by our data showing growth inhibition after addition of desferrioxamine, an iron chelator.
Some pathophysiological changes occurring in trauma patients could lead to increased E. coli growth in urine by a non-nutritional effect. There is a lower urea concentration in urine from trauma patients on day 1, in comparison with HV urine, which could be explained by the decrease in protein input and hypovolemia. Urea has an antibacterial effect, which is independent of osmotic pressure, but can also influence bacterial proliferation through osmotic pressure [9, 36].
The potential role of urinary catecholamines could be explained by their inhibitory effect on bactericidal activity of leukocytes  and by their own effect on bacterial multiplication [23, 38, 39]. Several studies have reported that catecholamines stimulate bacterial proliferation. However, these studies focused on gut flora and did not explore bacterial growth in the urinary tract. With low bacterial inoculum and during prolonged bacterial growth, Freestone et al. have shown a positive effect of norepinephrine on bacterial growth even at 1 μM, the mean concentration of norepinephrine in the TP urine . We could not demonstrate under our experimental conditions a positive and independent effect of norepinephrine on bacterial growth, suggesting that the effect of catecholamine alone is weak and requires the presence of iron to stimulate bacterial multiplication.
Finally, in 5 cases bacteria were present in the urine; they were in two cases P. mirabilis. These findings highlight the predisposition of trauma patients to develop asymptomatic bacteriuria.
Strengths of our study include i) its originality with a new concept which could contribute to high sensitivity of critically ill patients to infections; ii) the exploration of nutritional and non-nutritional way to facilitate bacterial growth; ii) the comparison between patients and healthy volunteers. However, our study has several limitations The list of metabolites that we studied is not exhaustive; for example, we did not explore interleukin (IL) urinary excretion, even though IL-1 is known to be excreted during acute kidney injury due to shock and is known to enhance E. coli growth [24, 40]. Eighteen patients received antibiotics at one stage of the study, making non interpretable some urine samples. The fact that the healthy volunteers did not have an indwelling bladder catheter may be a confounding factor, because the urinary catheter could change the urinary sediment or cause cellular damage. If further investigations are required to discriminate the potential role played by the urinary catheter, the trauma and shock remain the main cause of the increase in glycosuria, in amino acid excretion and in change in urea concentration.