Clinical recommendations for the inpatient management of lower respiratory tract infections in children and adolescents with severe neurological impairment

Clinical recommendations for the inpatient management of lower respiratory tract infections in children and adolescents with severe neurological impairment

  • Post category:Expert Opinion
  • Reading time:15 mins read

Introduction

(Article introduction authored by ICU Editorial Team)

Children and adolescents with severe neurological impairment (SNI) face complex medical challenges, often experiencing severe and recurrent lower respiratory tract infections (LRTIs).

These infections, caused by viruses and bacteria, pose a significant threat, leading to respiratory insufficiency and lasting impairments.

Expert consensus has guided the development of clinical recommendations for managing LRTIs in this patient population, emphasizing comprehensive multidisciplinary care and antibiotic stewardship. Initial treatment focuses on symptomatic care, including hydration, antipyretics, oxygen therapy, and respiratory support.

For bacterial LRTIs, antibiotic therapy is tailored to infection severity, recommending aminopenicillin plus a beta-lactamase inhibitor for community-acquired cases and piperacillin-tazobactam for those with chronic lung disease or tracheostomy.

Ongoing management involves regular assessments, adjustments based on pathogen identification, and optimizing supportive care.

Implementing these recommendations aims to enhance the diagnosis and treatment of LRTIs in children and adolescents with SNI.

Materials and methods

These recommendations were formulated on behalf of the German Society for Pediatric Infectious Diseases (DGPI) in accordance with the regulations of the AWMF (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften: working group of the German Scientific Medical Societies).

Six professional societies participated in their development, each nominating an expert in the field: DGKJ (German Society for Pediatrics and Adolescent Medicine), DGPI (German Society for Pediatric Infectious Diseases), DGP (German Society for Palliative Medicine), GNP (Society for Neuropediatrics), GNPI (Society for Neonatology and Pediatric Intensive Care Medicine), and GPP (Society for Pediatric Pneumology).

The literature search, conducted in September 2022, focused on pneumonia, lower respiratory tract infection, and neurological impairment in children.

The expert panel reviewed the literature, and treatment recommendations were drafted. Two online conferences were held in January 2023 for further discussion and consensus. After expert group approval, the recommendations underwent online consensus from the entire group.

The manuscript was submitted to professional societies for review, and the final version was sent to experts for approval.

The German version of the recommendations is published in the AWMF guideline register, and all expert group members disclosed potential conflicts of interest.

Results

Concerned patients and scope of the recommendations

This treatment recommendation primarily addresses the therapy of children with severe neurological impairment (SNI) who are hospitalized or in inpatient long-term care facilities, including those in residential settings for long-term ventilator-dependent patients or children’s hospices with specialist care.

Inpatient hospital treatment for these patients should be determined on an individual basis, considering criteria such as severe dyspnea, dehydration, prolonged recapillarization time, cyanosis, apnea, or impaired consciousness.

The recommendations apply to pediatric patients with motor and/or cognitive impairments requiring interdisciplinary and multimodal support in daily activities, encompassing those with severe cerebral palsy, neurodegenerative diseases, encephalopathies, syndromic diseases, progressive muscular or metabolic diseases, severe traumatic brain injury, or unfavorable courses of cerebral tumor disease.

Diagnostics

Clinical signs of lower respiratory tract infections (LRTIs) in children with severe neurological impairment (SNI) may include tachypnea, dyspnea, fever, cough, altered respiratory secretions, increased oxygen demand, or abnormal auscultation findings.

Nonspecific signs like gastrointestinal symptoms or decreased exercise tolerance can also occur. A comprehensive diagnostic workup is essential, considering potential septic shock.

Admission assessments should include a detailed history, vital signs, and laboratory tests, such as blood count, liver enzymes, creatinine, C-reactive protein, and blood gas analysis.

Blood cultures, obtained aseptically, are recommended in severe cases. Microbiological diagnostics involve deep respiratory secretions, ideally obtained by sputum or nasopharyngeal aspirate after hypertonic saline inhalation.

Tracheal secretions can be collected from tracheostomy. Screening for respiratory viruses and bacteria, including multidrug-resistant strains, is crucial.

Ultrasonography is recommended for suspected pleural effusion, and chest X-rays or CT scans may be considered based on clinical presentation and necessity. Regular evaluations and adjustments to therapy optimize patient care.

Initial treatment

Patients with severe neurological impairment (SNI) and lower respiratory tract infections (LRTIs) should receive comprehensive symptomatic therapy, including weight-adjusted hydration, antipyretics for fever, and respiratory support.

Oxygen therapy is recommended if transcutaneous saturation is below 92%, and bronchodilators and secretolytics can be used as needed.

Physiotherapeutic respiratory therapy is advised for retained secretions. In severe cases with respiratory insufficiency, consultation with pediatric pneumologists, infectious disease specialists, and intensive care specialists is crucial.

Pharmacological treatment, such as opioids, may be necessary for severe dyspnea. If there’s no clinical response to antibiotic therapy, a discussion should occur before switching or escalating treatment, considering other factors like inadequate secretion management.

Suspected viral LRTI

If influenza is strongly suspected, a 5-day course of oral oseltamivir should be initiated promptly.

The use of antiviral treatment for influenza in this population is still debated. Treatment of SARS-CoV-2 infection should follow current guidelines.

In cases of clinical deterioration, re-evaluation for bacterial coinfection is recommended after 48–72 hours, with a focus on common pathogens like pneumococci and S. aureus post-influenza.

Suspected bacterial LRTI

Initial antibiotic therapy (ABT) for lower respiratory tract infections (LRTIs) is classified into groups. Group I, comprising patients with community-acquired LRTI or aspiration pneumonia, is recommended to receive aminopenicillin plus a beta-lactamase inhibitor.

This combination effectively treats common pathogens causing childhood pneumonia. Group II patients, including those with chronic lung disease, tracheostomy, and recurrent LRTIs, are advised to undergo initial therapy with piperacillin-tazobactam, offering increased efficacy against gram-negative bacteria, beta-lactamase-producing isolates, and P. aeruginosa.

Penicillin-resistant pneumococci may require alternative therapies like ceftriaxone or vancomycin.

Critically ill patients, irrespective of group classification, should receive primary treatment with piperacillin-tazobactam.

In cases of septic shock or sepsis with multiple organ failure accompanying lower respiratory tract infection (LRTI), initial therapy is recommended with meropenem plus vancomycin.

For patients with severe neurological impairment (SNI) and LRTI colonized with methicillin-resistant Staphylococcus aureus (MRSA) who are not critically ill, MRSA coverage is necessary only in the presence of complicated LRTI or if the MRSA isolate expresses Panton-Valentine leukocidin (PVL).

The choice of antibiotics should consider the resistogram, and critical care patients with SNI and LRTI colonized with MRSA may be empirically treated with vancomycin or linezolid, with a potential transition to targeted monotherapy after an “antibiotic timeout”.

Ongoing management

After 48–72 hours of antibiotic therapy, a critical evaluation known as an “antibiotic timeout” should be conducted. This involves reviewing the initial indications and assessing the ongoing therapy.

Planning for the timeout should occur upon admission, ideally involving an infectious disease consultation.
All relevant information, including clinical response, imaging results (X-ray/CT), laboratory findings, and microbiological results, should be gathered and considered.

This comprehensive review helps reevaluate the likelihood of bacterial infection and guides further diagnostic and therapeutic decisions.

If the patient’s clinical condition improves

If bacterial infection is considered unlikely during the “antibiotic timeout,” ABT should be discontinued.

If a bacterial infection is suspected and the patient’s condition improves under the initiated therapy, then the ABT should be adapted where feasible to target the specific pathogen that may have been detected (e.g., penicillin, ampicillin, or amoxicillin instead of ampicillin-sulbactam).

ABT can also be changed from intravenous to oral therapy (respectively, therapy via gastral tube) if possible.

If the patient’s clinical condition remains poor

If the patient’s condition remains persistently poor, comprehensive efforts should be undertaken to enhance all aspects of supportive care, encompassing interventions such as inhalation, secretolysis, physical therapy, positioning treatment, respiratory and cough support, dyspnea management, and pain control.

In the presence of new relevant clinical or imaging findings, consideration should be given to alternative diagnoses or potential complications.

Consultation with infectious diseases and/or pulmonary specialists may guide further assessments, including repeat chest X-rays or ultrasound to evaluate for pleural empyema.

Bronchoalveolar lavage may be required for pathogen detection, and if significant resistogram results are obtained, a targeted adjustment of antibiotic therapy should be implemented.

Specifically, for lower respiratory tract infections caused by Pseudomonas spp., piperacillin-tazobactam should be administered every 6 hours, and if vascular access allows, the infusion duration should be extended to 3–4 hours per administration.

This approach aims to optimize care and address specific challenges associated with persistent or complicated cases of lower respiratory tract infections.

If the patient’s clinical condition worsens significantly

If the patient’s condition significantly worsens during therapy, a comprehensive optimization of supportive care, including interventions such as inhalation, secretolysis, physical therapy, positioning treatment, respiratory and cough support, dyspnea management, and pain control, should be prioritized.

If respiratory specimens reveal pathogen detection and resistogram results are available, a targeted adjustment of antibiotic therapy (ABT) is recommended.

In cases where no pathogens are detected, therapy should be escalated. For group I patients initially treated with an aminopenicillin plus beta-lactamase inhibitor, switching to piperacillin-tazobactam is advised.

For group II patients previously treated with piperacillin-tazobactam, the selection of escalation options should be tailored to individual patient considerations.

Factors such as severe peripheral neuropathy, pre-existing renal dysfunction, or sensorineural hearing loss may contraindicate the use of aminoglycosides.

Table 2 outlines alternative options, emphasizing a judicious approach to meropenem use. Ciprofloxacin is recommended as the preferred fluoroquinolone for Pseudomonas aeruginosa infections.
Caution is warranted in the use of fluoroquinolones in children, considering concerns about long-term selection of multidrug-resistant bacteria and potential neurotoxicity.
Inclusion of fluoroquinolones in this context emphasizes the need for cautious and informed use, particularly in children and adolescents with severe neurological impairment treated as outpatients.

Duration of antimicrobial therapy

Antibiotic therapy, with clinical efficacy usually seen after 48–72 h, should be given for 5–7 days in patients with SNI. A longer duration may be required in complicated LRTI (e.g., parapneumonic effusion and pleural empyema) or depending on clinical response. For bronchiectasis, a duration of 10–14 days is recommended. Sequential oral therapy is possible according to the results of the resistogram.

Prevention of (recurrent) LRTIs and considerations for future treatments

Children and adolescents with severe neurological impairment (SNI) experiencing recurrent bacterial lower respiratory tract infections (LRTIs) may benefit from inhalation therapy with agents like tobramycin or colistin for prophylaxis or pathogen eradication.

Vaccinations against common bacterial LRTI pathogens are essential to prevent invasive infections and combat antibiotic resistance.

A defined strategy for empiric antibiotic therapy (ABT) should be established and accessible to medical personnel caring for these patients.

In cases where oral medications have proven ineffective, early implantation of a long-term central venous access device can be considered.

The ethical and palliative care aspects of treating children and adolescents with severe neurological disorders are crucial. The overarching goal is to maximize their quality of life until the end.

Palliative and symptom-relieving therapy takes precedence in life-threatening crises, with decisions made through participatory consultations involving patients, legal guardians, or caregivers.

Specialized palliative care, involving clinical ethics committees, palliative physicians, and support from various professionals, ensures holistic, family-centered support.

Therapeutic limitations should be considered when interventions may excessively burden the patient without overcoming acute medical deterioration.

Advance care planning (ACP) is crucial for patients with SNI, involving discussions about treatment preferences during different phases of disease deterioration.

An “advance declaration on emergency situations” can predefine treatment preferences to guide caregivers or patients capable of giving consent.

Summary of recommendations

Managing the medical needs of children and adolescents with severe neurological impairment (SNI) requires a comprehensive multidisciplinary approach.

The provided recommendations offer age-specific guidance for diagnosing and treating lower respiratory tract infections (LRTIs) in this population.

Symptomatic therapy, including inhalation, secretolysis, physiotherapy, positioning, and pain therapy, is essential. Adequate medical and microbiological diagnostics, considering possible differential diagnoses, are emphasized.

The initiation of antibiotic therapy (ABT) should involve an “antibiotic timeout” after 48–72 hours, with a multidisciplinary team re-evaluating the indication and therapy. Aminopenicillin plus a beta-lactamase inhibitor is recommended for suspected bacterial LRTI, while piperacillin/tazobactam is considered for patients with chronic lung disease or recurrent LRTIs. Repeated “antibiotic timeouts” should reassess the ABT indication, and adjustments based on microbial findings may involve an intravenous-to-oral switch.

The presence of a respiratory virus does not exclude bacterial (co-)infection. In cases of no improvement, symptomatic therapy optimization is prioritized, followed by empirical therapy escalation in the absence of pathogen evidence.

Discussion

The antibiotic therapy (ABT) rationale in these recommendations draws from experiences in treating cystic fibrosis (CF) patients, considering pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, and Enterobacteriaceae.

However, a cautious approach is advised, as applying intensive ABTs used in CF to all severe neurological impairment (SNI) patients may risk long-term selection of multidrug-resistant (MRD) bacteria. Empiric therapy options cover common bacterial CAP pathogens, S. aureus, and many Gram-negative bacteria. If initial therapies fail and the pathogen is undetected, an insufficiently treated Gram-negative pathogen is assumed.

This rationale supports expanding the spectrum of activity, either by switching to piperacillin-tazobactam or further expanding its Gram-negative spectrum.

Combination therapy with tobramycin or fosfomycin is considered based on favorable evidence from CF therapy.

Extended infusion of beta-lactam antibiotics and levofloxacin is proposed as alternative treatment choices. Inhaled antibiotic therapy, especially with tobramycin, can aid acute treatment.

Beyond established immunizations, future options against respiratory syncytial virus (RSV) are recommended to prevent severe LRTIs.

Source: Mauritz, M.D., von Both, U., Dohna-Schwake, C. et al. Clinical recommendations for the inpatient management of lower respiratory tract infections in children and adolescents with severe neurological impairment in Germany. Eur J Pediatr (2024). https://doi.org/10.1007/s00431-023-05401-6