In this large retrospective study on pediatric LNB patients, we have shown that there was no difference between children, independent of age, who had received ceftriaxone i.v. and those who had received doxycycline p.o. when comparing clinical outcome (recovery/non-recovery). Our results are in line with previous studies (17), supporting the hypothesis that doxycycline p.o. is as effective as ceftriaxone i.v. for treatment of LNB. However, the efficacy and safety of the two different treatment strategies could not fully be evaluated in our study, since it was not a randomized comparative study, and unknown confounding factors may have influenced our results.
One strength of our retrospective study was that results are based on data from a relatively larger patient sample (n=321) including three previous prospective cohorts. Patients are well characterized and considered representative of Swedish pediatric LNB patients, and all participating children were clinically followed-up at 2 months, in all three cohorts. The follow-up visits were congruent and well executed by physicians at each pediatric department, including a clinical examination and a pre-defined structured questionnaire for self/parent-reported persistent symptoms. Patients were defined as being recovered/not-recovered based on findings from the examination and answers from the questionnaires. Unfortunately, for the assessment of clinical outcome, no clinical composite score nor validated questionnaire was used at the follow-up visits, which is a weakness of the study. However, we believe that the overall clinical evaluation of each patient, by pediatricians at the 2-month follow-up visit, was correct and sufficient to determine if the patient was recovered/not-recovered.
An additional limitation of the study is that we did not have precise data on the duration of antibiotic treatment, since children could have received a course of antibiotic treatment varying from 10 to14 days. Therefore, analysis of the association between treatment duration and clinical outcome was not feasible.
The duration of antibiotic treatment in children with early LNB has been under debate (21) and treatment for 10-30 days has been suggested (17, 22). Recently published evidence-based guidelines from Germany have determined a recommendation of 14 days of doxycycline, ceftriaxone, cefotaxime or Penicillin G i.v. (21).
The age of the children and the choice of antibiotic treatment was not always congruent with Swedish guidelines in our study. Thirtyeight (n=38) children had received ceftriaxone i.v. even though they were ≥ 8 years of age.These patients could possibly have had a more severe LNB on admission than other children. However, with the regression analysis, including age, symptoms on admission and antibiotic treatment, this should not have influenced our results on clinical outcome.
The most common persistent symptom at the 2-month follow-up in our study was facial nerve palsy (16%). Results were similar in both diagnostic groups (Definite LNB and Possible LNB) and in both treatment groups (ceftriaxone i.v. and doxycycline p.o.). Results are in line with previous studies (9, 23). Facial nerve palsy on admission was also one of the major clinical manifestations associated with a higher risk of non-recovery in our logistic multivariate regression analysis. This result is not surprising, and in line with earlier studies, where the validated House-Brackmann grading scale has also been used to evaluate clinical outcome (23, 24). However, the manifestation of fever on admission and its association with poorer clinical outcome was more surprising. This association could possibly be understood, as the fever itself being a sign of strong immunological activity in CSF in LNB, and the inflammation could negatively influence both the ability of clearing symptoms and clinical outcome (25). Anti-Borrelia antibodies in CSF were, contrary to facial nerve palsy and fever, associated with a better clinical outcome, possibly because of a faster and more determined decision for the start of treatment by the pediatricians in charge, which could have been beneficial for clinical recovery (9). Admittedly, the discussion about these associations is somewhat speculative and in some measure difficult to explain from a pathophysiological point of view, and should be interpreted with caution.