The most common and lethal bacterial pathogens have co-evolved with the host. Pathogens are the aggressors, and the host immune system is responsible for the defence. However, immune responses can also become destructive, and excessive innate immune activation is a major cause of infection-associated morbidity, exemplified by symptomatic urinary tract infections (UTIs), which are caused, in part, by excessive innate immune activation. Severe kidney infections (acute pyelonephritis) are a major cause of morbidity and mortality, and painful infections of the urinary bladder (acute cystitis) can become debilitating in susceptible patients. Disease severity is controlled at specific innate immune checkpoints, and a detailed understanding of their functions is crucial for strategies to counter microbial aggression with novel treatment and prevention measures. One approach is the use of bacterial molecules that reprogramme the innate immune system, accelerating or inhibiting disease processes. A very different outcome is asymptomatic bacteriuria, defined by low host immune responsiveness to bacteria with attenuated virulence. This observation provides the rationale for immunomodulation as a new therapeutic tool to deliberately modify host susceptibility, control the host response and avoid severe disease. The power of innate immunity as an arbitrator of health and disease is also highly relevant for emerging pathogens, including the current COVID-19 pandemic.
A, Chao S-M. Treatment of urinary tract infection with gentamicin once or three times daily. Acta Paediatr 2003; 92: 291-296. Stockholm. ISSN 0803-5253 Aim: To examine the safety and efficacy of once-daily (OD) gentamicin treatment compared with conventional 8-hourly dosing (TDS) for urinary tract infection (UTI). Methods: This was a prospective, randomized, controlled trial of children 1 mo to 13 y of age with presumed UTI. Children were randomly assigned to OD gentamicin 5 mg kg À1 d À1 or TDS gentamicin 6 mg kg À1 d À1 divided 8 hourly. Microbiological efficacy, nephrotoxicity, ototoxicity and renal scarring were assessed at the end of treatment. Results: 210 patients with presumed UTI were recruited, of whom 172 were analysable (OD 84, TDS 88). The median age was 7 mo, 50% were male and 74% (n = 127) of patients had pyelonephritis. The majority of infections were due to Escherichia coli (n = 153, 89%), of which 9 (5.2%) were bacteraemic. Comparing the two groups, there was no significant difference in age, gender, duration of fever before admission, pyuria, nitrite positivity or initial total white blood cell count. All patients had negative urine cultures after 2-3 d of treatment, demonstrating 100% microbiological efficacy. There was no difference between the two groups in terms of ototoxicity, nephrotoxicity, duration of gentamicin treatment or time to fever defervescence.Conclusion: OD gentamicin is as efficacious as TDS gentamicin in the treatment of UTI in children, with no difference in ototoxicity and nephrotoxicity.
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