Particularitățile terapiei antimicrobiene în pneumonia comunitară la copii, inclusiv bronhopneumonia

Introduction

Infectious diseases remain a significant threat to global child health, with community-acquired pneumonia (CAP) and bronchopneumonia, that represent one of the most common and deadly conditions in pediatric populations. Pneumonia in children – a broad term for lung inflammation – is a type of pneumonia characterized by inflammation of the lung tissue, causing alveoli to fill with fluid or pus, and it includes lobar pneumonia (affecting a large section/lobe) and bronchopneumonia – a specific form of pneumonia, characterized by patchy inflammation that starts in the bronchi and spreads to surrounding alveoli, often affecting both lungs. From a clinical and morphological perspective, pneumonia encompasses several forms, among which bronchopneumonia represents a frequent presentation in pediatric patients. Bronchopneumonia is not a distinct nosological entity, but rather a form of acute community-acquired pneumonia, that remains one of the leading causes of morbidity in children worldwide, accounts for a substantial proportion of hospital admissions and childhood mortality. Although widespread immunization against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) has reduced disease incidence, the burden remains considerable, particularly in regions with limi­ted healthcare access^(1-3). The cornerstone of management for bacterial pneumonia in children is antimicrobial therapy. However, increasing antimicrobial resistance, variability in etiological agents, and challenges in distinguishing viral from bacterial infections complicate antibiotic prescribing^(4-9). Inappropriate antibiotic use contributes to treatment failure and adverse drug reactions, exacerbating the global crisis of antimicrobial resistance^(10-12). Consequently, a judicious, evidence-based approach to antibiotic therapy is imperative.

This article aims to elaborate a comprehensive review of antimicrobial administration in pediatric acute community-acquired pneumonia, including bronchopneumonia, focusing on etiology, clinical presentation, diagnostic approaches, pharmacotherapy, resistance mechanisms and stewardship strategies. By integrating pharmacological principles with clinical guidelines, this review seeks to support rational antibiotic use and optimize therapeutic outcomes in children^(4-6,11-14).

Etiology of pediatric bronchopneumonia

CAP – including bronchopneumonia – in children is primarily caused by infectious agents, with etiological agents varying by age, immunization status and geographic region^(2,4,15-17).

Bacterial pathogens.Streptococcus pneumoniae remains the most common across the pediatric population^{(2,4,15,17,18)}. Haemophilus influenzae type b remains a significant pathogen in unvaccinated populations, while non-typeable H. influenzae contributes to disease in vaccinated settings^(1,17). Staphylococcus aureus, including methicillin-resistant strains (MRSA), is associated with severe disease and necrotizing pneumonia, especially following viral upper respiratory infections such as influenza^(19,20). Other noteworthy bacterial agents include Gram-negative organisms such as Escherichia coli and Klebsiella pneumoniae, which are typically associated with infections in newborns and immunocompromised hosts^(21,22), and Moraxella catarrhalis, which is more commonly observed in younger children⁽¹⁵⁾. Aty­pi­cal pathogens such as Mycoplasma pneumoniae and Chlamydophila pneumoniae are more prevalent in school-aged children and adolescents. Chlamydia trachomatis is linked to afebrile pneumonia in infants, usually acquired perinatally^(23-25).

Viral pathogens. The most common viral cause of lower respiratory tract infections in infants is respiratory syncytial virus (RSV), which frequently manifests as bronchiolitis or pneumonia⁽¹⁶⁾. Other important viral pathogens include adenovirus, rhinovirus, human metapneumovirus, influenza A and B, and parainfluenza viruses^(16,26). These viral agents may act alone or in synergy with bacteria, complicating both diagnosis and treatment. In many settings, viral-bacterial coinfection is common in children hospitalized with pneumonia^(7,15,16,27).

Fungal etiology. Although uncommon in immunocompetent children, fungal infections can occur in immunocompromised individuals. Pneumocystis jirovecii is an important opportunistic pathogen, especially in children with HIV/AIDS or other immunosuppressive conditions^(21,28). Different fungal species, such as Candida spp., Aspergillus spp. and Histoplasma capsulatum, are usually associated with severe or widespread illness^(28,29).

Host and environmental determinants of etio­logy. Children are susceptible to community-acquired pneumonia, including bronchopneumonia, due to multiple host and environmental factors. These include inadequate vaccination status, neurological problems that limit airway clearance, prematurity, congenital abnormalities of the respiratory or circulatory systems, and malnutrition^(28-31). Respiratory infection risk is also significantly increased by exposure to air pollution, tobacco smoke and crowded living conditions^(30-32).

Accurate diagnosis, suitable antibiotic treatment and effective preventive measures in pediatric populations depend on understanding this complex etiologic landscape^(2,8,17,32).

Epidemiology and risk factors

Global burden. CAP, including bronchopneumonia, remains a leading cause of pediatric morbidity and mortality, particularly in children under 5 years of age. Despite improvements in vaccine coverage and access to antibiotics, the burden of CAP and bronchopneumonia remains high in both low- and middle-income countries (LMICs) and in underserved populations in high-income regions, including parts of Eastern Europe^{(1,2,17,32,33)}. Globally, the World Health Organization (HWO) estimates that pneumonia accounts for approximately 15% of all deaths in children under 5, with the highest incidence occurring in sub-Saharan Africa and South Asia^(1,31-33).

Regional examples. Significant regional disparities persist. In low-resource countries, community-acquired pneumonia is among the top causes of under-5 mortality, with malnutrition, incomplete immunization, indoor air pollution and poor housing conditions as significant risk factors^(2,8,30,32). In India and other LMICs, large-scale cohort studies have consistently shown that younger age (especially under 2 years old), low weight-for-height, stunting and lack of exclusive breastfeeding significantly increase the risk of severe pneumonia^(8,30,32). Chronic illnesses, congenital defects and immunodeficiency in both high- and low-resource environments (e.g., HIV infection, asthma and congenital heart disease) significantly raise the chance of developing serious illness^(21,28-31).

Individual-level risk factors. The highest disease burden is observed in low- and middle-income countries, where socioeconomic disparities, malnutrition, incomplete immunization and environmental exposures increase susceptibility^(2,8,30,32). Key risk factors include: young age (especially Pneumococcus, Hib, measles, pertussis and influenza^{(1,2,17,21,28,30-32)}.

These determinants highlight the multifactorial nature of disease risk and the importance of preventive public health strategies^{(1,4,6,8,11,12,29,31)}.

Clinical features and diagnostic approaches

Clinical manifestations of CAP and bronchopneumonia range from mild respiratory symptoms to severe respiratory distress. Standard features include fever, cough, tachypnea (rapid breathing), dyspnea (shortness of breath), chest retractions and crackles and wheezing. Infants may present with nonspecific signs such as poor feeding, lethargy, or irritability^{(5,7,8,13,14,15,17)}.

Severity and risk factors. CAP, including bronchopneumonia, is a significant cause of morbidity and mortality in the pediatric population, particularly in children under 5 years of age^{(2,5,7,17,30-32)}. The severity of infection affects clinical manifestations^(5,6,8,16). Children with CAP frequently exhibit chills and rigors along with high-grade fever^(5,7). Respiratory symptoms include tachypnea, dyspnea and increased work of breathing, which can manifest as grunting, intercostal and subcostal retractions, and nasal flaring^(5,6). Many patients report a cough that may produce purulent sputum. Crackles and wheezes are commonly auscultated due to secretions and airway inflammation^(5,6,33). Pleuritic chest pain may worsen with coughing or deep breaths^(5,6). Systemic symptoms like tachycardia, exhaustion, irritability, anorexia and dehydration are frequently observed^(7,8). Nonspecific symptoms such as lethargy, poor feeding, vomiting and a “toxic” appearance should raise clinical suspicion for bronchopneumonia in infants and young children^(2,8,17,31).

Diagnostic process. A comprehensive clinical history and physical examination by the physician are the first steps in the diagnosis process^(5,6). The assessment focuses on respiratory rate, oxygen saturation, auscultatory results, and indications of respiratory distress^(5,6,14). Supplementary investigations are necessary to validate and assess disease severity. Chest radiography is foundational for diagnostic imaging, showing distinctive patchy infiltrates consistent with bronchopneumonia^(33-35). It helps distinguish bronchopneumonia from other pulmonary diseases, such as viral bronchiolitis, lobar pneumonia or atelectasis^(6,33-35). Chest radiography is essential for identifying characteristic patchy infiltrates associated with bronchopneumonia and for distinguishing it from other patterns such as lobar pneumonia or interstitial infiltrates^(33-35).

Lung ultrasound is an acceptable alternative diagnostic imaging modality when standard chest radiography or computed tomography (CT) is not readily available and clinical staff have received appropriate training in POCUS (point-of-care ultrasound). Lung ultrasound is sensitive for detecting consolidation, pleural effusions, and pneumothorax and may reduce radiation exposure; however, its use should be guided by institutional expertise and clinical protocols.

Laboratory and advanced diagnostics. Laboratory tests include complete blood counts to identify leukocytosis or leukopenia^(7,8). Blood cultures, although often negative in simple cases, can detect systemic bacteremia^(5-7,22,25). In some instances, nasopharyngeal swabs or sputum cultures aid in isolating pathogens^{(7,15,16,20,22)}. Bronchoscopy may be necessary in severe or complex cases to visualize the airway, collect samples from the lower respiratory tract, or remove obstructive secretions⁽⁶⁾. In critically ill children, arterial blood gas analysis may be required to evaluate respiratory compromise and acid-base status, while pulse oximetry is crucial for non-invasive oxygen saturation monitoring^(4-6).

Emerging diagnostic techniques. Polymerase chain reaction (PCR) for respiratory pathogens is an emerging diagnostic technique that enhances the accuracy of etiological diagnosis, allows differentiation between viral and bacterial causes, and minimizes unnecessary antibiotic use. Biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) may support decisions regarding the initiation or discontinuation of antibiotics and the duration of therapy. However, pediatric-specific evidence is still evolving^(7,16,17,36).

In summary, diagnosing CAP – including bronchopneumonia – in children is a complex process that requires focused research and clinical assessment. Early detection and timely treatment are essential to reduce morbidity and mortality associated with this prevalent but potentially fatal illness^{(1,2,4,16,17,32)}.

Differential diagnosis of CAP and bronchopneumonia

CAP and bronchopneumonia may mimic or overlap with other conditions, such as viral pneumonia (including influenza and COVID-19), tuberculosis, aspiration pneumonia, noninfectious inflammatory disorders (e.g., organizing pneumonia), pulmonary tumors, interstitial lung diseases and pulmonary embolism. Accurate differentiation relies on careful clinical assessment, chest imaging, microbiological tests and, in selected cases, advanced imaging or histopathology is requested^{(4-6,17,34,35)}.

Treatment and principles of antibiotic therapy

The management of pediatric CAP, including bronchopneumonia, is predicated on two pillars: optimized supportive care and judicious antimicrobial therapy where bacterial infection is suspected or confirmed. The latter must be informed by pediatric-specific pharmacologic principles^(4-6,11-13).

Supportive and non-antimicrobial management

Supportive care is fundamental, regardless of etio­logy^{(2-6,14,23,24)}.

• Nutritional support, including targeted management of acute malnutrition when present: oral fluids preferred; avoid overhydration; i.v. fluids only if the patient is unable to drink, in case of severe respiratory distress or shock^(1,5,14).
• Oxygen supplementation to maintain SpO₂ ≥92-94%, administered via low-flow nasal cannula, high-flow nasal cannula, or noninvasive ventilation as appropriate.
• Fluid management, balancing the risks of dehydration and fluid overload; oral rehydration is preferred when feasible, with intravenous fluids reserved for children unable to maintain adequate intake.
• Antipyretics, such as paracetamol, for fever control and comfort.

For confirmed viral pneumonia without evidence of bacterial superinfection, antibiotics are not indicated. Antiviral agents (e.g., neuraminidase inhibitors such as oseltamivir) may be used for influenza in high-risk or severely ill children^(16,26,37).

Indications for antibiotic therapy and risk-stratified approach

Antibiotic therapy is indicated in the following clinical scenarios:

• Confirmed or highly suspected bacterial CAP and bronchopneumonia based on clinical presentation, radiologic findings, or microbiological evidence (positive blood culture, sputum culture, or PCR) and/or laboratory findings.
• Severe illness where bacterial infection cannot be reliably excluded, and the risk of adverse outcomes is significant
• High risk of bacterial superinfection, such as in severe influenza or documented post-viral deterioration with clinical worsening^(5,6,26,28).

In immunocompetent, fully vaccinated children with mild-to-moderate community-acquired pneumonia, the decision to initiate empirical antibiotic therapy should be risk-stratified^{(1,4,16,19,22)}. Children with mild to moderate community-acquired pneumonia, including bronchopneumonia, may be safely managed in the outpatient setting, provided that there are no signs of respiratory distress, hypoxemia, or complications.

• Outpatient management without comorbidities: if a positive respiratory viral test (influenza, RSV, SARS-CoV-2, etc.) is confirmed and the child has no significant comorbidities (asthma, chronic lung disease, congenital heart disease, immunodeficiency), empiric antibiotics are conditionally not recommended (very low-quality evidence). This represents a shift from prior guidance and reflects lower concern for bacterial-viral coinfections in immunocompetent hosts.
• Outpatient management with comorbidities: empiric antibiotics are conditionally recommended if underlying chronic illness (asthma, cystic fibrosis, immunodeficiency), prematurity, or other risk factors elevate the probability of bacterial coinfection.
• Hospitalized children: empiric antibiotic therapy is conditionally recommended for all hospitalized children with suspected CAP or bronchopneumonia, due to potential for severe disease and co-infection, regardless of viral testing results.

Diagnostic support for empiric decisions. Emerging molecular diagnostics (PCR for respiratory pathogens), procalcitonin (PCT) and C-reactive protein (CRP) can support initiation and de-escalation decisions. Procalcitonin thresholds (e.g., below 0.25-0.5 ng/mL in some pediatric settings) may support withholding or early discontinuation of antibiotics in low-risk patients with viral infections. However, pediatric-specific biomarker cutoff values require further validation, and clinical judgment should remain paramount^(5,6,36).

Empirical antibiotic regimens. Current antimicrobial recommendations are based on the management of community-acquired pneumonia. These therapeutic principles are applicable to bronchopneumonia, as it represents a common clinical form of community-acquired pneumonia in children. The principles of empirical selection include coverage of likely pathogens, alignment with local resistance patterns, preference for narrow-spectrum agents when appropriate, and consideration of comorbidities and drug interactions^{(4-6,16,17,36,38,39)}.

Outpatient therapy (mild to moderate CAP, including bronchopneumonia). For immunized children aged 3 months to 5 years old with suspected bacterial pneumonia and no significant comorbidities, first-line therapy typically includes high-dose amoxicillin^{(5,6,36,38,39)}. In cases of nonanaphylactic penicillin allergy, an oral second-generation cephalosporin may be employed.

Inpatient therapy (moderate to severe CAP, including bronchopneumonia). In fully immunized children in settings with low to moderate penicillin resistance, intravenous ampicillin or penicillin G is recommen­ded^{(4-6,13,16,17,36)}. When local pneumococcal resistance is high, the child is not fully immunized, or the disease is severe, third-generation cephalosporins such as ceftriaxone or cefotaxime are often preferred^{(4-6,8,9,13,17,18,36)}.

If methicillin-resistant Staphylococcus aureus (MRSA) is suspected – based on necrotizing pneumonia, post-influenza deterioration, presence of empyema, or severe sepsis –, anti-MRSA coverage with vancomycin or clindamycin is warranted^(5,6,19,20). In neonatal pneumonia, empirical regimens commonly combine ampicillin with an aminoglycoside (e.g., gentamicin), providing coverage for Group B Streptococcus and Gram-negative bacilli typical of early-onset sepsis^{(20,22,25,40)}.

Special consideration: macrolide use in pediatric CAP

Macrolide antibiotics (azithromycin, clarithromycin) should not be used as routine first-line therapy or for empirical dual therapy in pediatric CAP. However, they have a defined role in specific clinical scenarios and warrant careful consideration of both indications and resistance implications.

When macrolides are indicated: macrolides are conditionally recommended (low-to-moderate quality evidence) for children, particularly school-aged children and adolescents, with clinical or epidemiologic features suggestive of atypical bacterial pathogens-specifically Mycoplasma pneumoniae or Chlamydophila pneumoniae^{(5,6,15,19,23,24)}. Clinical indicators supporting an atypical infection include a prolonged or subacute cough, gradual clinical progression, mild respiratory findings on examination with fever, skin (maculopapular erythematous rashes) and mucous manifestations, endemic prevalence of atypical pathogens in the region, or compatible chest imaging patterns. In these settings, either macrolide monotherapy (e.g., azithromycin 10 mg/kg/day on day 1, then 5 mg/kg/day for days 2-5) or combination therapy with a b-lactam may be employed, depending on severity)^{(4-6,15,19,23,24,41)}.

When macrolides should NOT be used: routine dual therapy (b-lactam + macrolide) in nonsevere hospitalized CAP is not recommended in the absence of specific clinical or epidemiologic evidence of atypical infection^(5,6,24,25). Empirical use in young children (below 5 years old) without clinical suspicion of atypical pathogens, as S. pneumoniae remains the predominant pathogen, and macrolides provide inadequate coverage. In regions with high macrolide resistance, where more than 40-50% of S. pneumoniae isolates are resistant to macrolides, empirical use is particularly inadvisable.

Resistance concerns and clinical judgment. Unnecessary or prolonged macrolide use increases the risk of resistance in both S. pneumoniae and M. pneumoniae, which may result in future treatment failure and persistence of resistant organisms in the community^{(2,4-6,10-12)}. Additionally, unnecessary broadening of the antimicrobial spectrum disrupts the gut microbiome and increases the risk of Clostridioides difficile infection. Therefore, macrolide use must be reserved for clinical scenarios where atypical pathogen coverage is reasonably anticipated, and de-escalation to b-lactam monotherapy should be considered once microbiological data exclude atypical infection or once clinical response is evident^(5,6,42-44).

Pharmacokinetic and pharmacodynamic considerations

Pediatric patients exhibit profound age-dependent variability in drug disposition and response, necessitating tailored dosing strategies^{(22,40,42-44)}.

Age-dependent pharmacokinetics

Key developmental pharmacokinetic features include altered absorption in neonates and young infants; higher total body water and lower body fat, increasing the volume of distribution for hydrophilic drugs (e.g., b-lactams, aminoglycosides); maturational changes in hepatic metabolism; and delayed maturation of renal elimination. These maturational changes confer substantial inter- and intra-age group variability in half-life, peak concentration and exposure (AUC – aria under the curve), making age- and weight-specific dosing indispensable. Because many renally eliminated or hydrophilic agents (for example, vancomycin and several b-lactams) are cleared more rapidly in older infants and children than in adults, recommended mg/kg doses in pediatrics are sometimes higher than adult doses to achieve comparable ratio of the area under the concentration-time curve to the minimum inhibitory concentration (AUC/MIC) or trough targets^{(22,38,40,42-45)}.

Pharmacodynamic targets

Different antibiotic classes are characterized by distinct pharmacokinetic-pharmacodynamic (PK/PD) indices associated with efficacy^(38,44,46).

Beta-lactams (penicillin, cephalosporin): time-dependent bactericidal activity; efficacy correlates with the proportion of the dosing interval for which free drug concentrations exceed the minimum inhibitory concentration (ƒT>MIC). Pediatric regimens often employ higher mg/kg doses and more frequent dosing to maintain adequate ƒT>MIC. In practice, this concept underpins the use of prolonged or even continuous infusions of agents such as piperacillin-tazobactam, meropenem, or third-generation cephalosporins in critically ill children in PICU or in high-resistance settings, where increased volume of distribution and enhanced clearance would otherwise make it challenging to sustain concentrations above the MIC throughout the dosing interval^{(22,38,40,42,43,46)}.

Macrolides: primarily AUC/MIC-dependent effects with concentration-dependent killing at higher exposures. Extensive tissue penetration and prolonged half-life (especially with azithromycin) permit once-daily dosing schedules⁽⁴¹⁾.

Aminoglycosides: concentration-dependent bactericidal activity with a pronounced post-antibiotic effect; the peak/MIC ratio is a critical determinant of efficacy. Extended-interval (“once-daily”) dosing is frequently used but must be carefully adjusted based on age and renal function; TDM is recommended, particularly in neonates and critically ill children^(38,40).

Vancomycin: efficacy is best predicted by the AUC/MIC ratio; in children, higher mg/kg doses are often required to achieve target AUC values due to higher clearance. There has been a shift towards AUC-guided dosing, although in many pediatric centers, trough concentrations remain used as a pragmatic surrogate when formal AUC monitoring is not feasible⁽⁴³⁾.

Therapeutic drug monitoring (TDM) in resource-limited settings

While AUC/MIC-guided vancomycin dosing and extended-interval aminoglycoside dosing are the gold standard in centers with access to rapid TDM and pharmacokinetic expertise, many LMIC settings and resource-constrained facilities lack laboratory infrastructure for real-time concentration monitoring. In such contexts, age- and weight-based dosing nomograms, extended-interval dosing strategies, and standardized monitoring protocols (renal function, clinical response, signs of toxicity) provide practical alternatives. For vancomycin: empirical higher mg/kg doses (15-20 mg/kg/dose i.v. every 8-12 hours initially, with adjustment based on clinical response and serum creatinine trends) can approximate AUC targets without formal TDM. For aminoglycosides, once-daily extended-interval dosing (e.g., gentamicin 7.5 mg/kg i.v. daily in children >1 month old) reduces nephrotoxic accumulation and is feasible even without TDM, though renal function monitoring remains essential. Where TDM is available, it should be prioritized for critically ill children, neonates and those with renal impairment or comorbidities affecting drug clearance.

Dosing peculiarities

Practical aspects of pediatric dosing include mandatory weight-based dosing, attention to maximum daily doses, dose adjustments in renal and hepatic impairment, particularly for renally cleared drugs (aminoglycosides, vancomycin, many b-lactams) and consideration of obesity, which may alter distribution and clearance. Depending on the agent, dosing based on ideal body weight, total body weight, or adjusted body weight may be appropriate. In obese children, hydrophilic drugs such as b-lactams and aminoglycosides may not distribute proportionally to total body weight, and using ideal or adjusted body weight can help avoid both under-exposure and accumulation^(44-47).

In children with significant comorbidities, PK/PD considerations become particularly relevant. Those with cystic fibrosis often have increased clearance and larger volumes of distribution, so antipseudomonal b-lactams and aminoglycosides may require higher mg/kg doses and, in some cases, more frequent administration to achieve therapeutic levels. Conversely, in children with renal impairment, or in those with severe malnutrition or neuromuscular disease in which serum creatinine underestimates renal dysfunction, doses and intervals for renally cleared drugs must be individualized and, where available, guided by therapeutic drug monitoring to balance efficacy and toxicity^{(22,38,40,42-44,46,47)}.

In severe bronchopneumonia, sepsis or PICU admission, these PK/PD principles often translate into using the upper end of recommended mg/kg dosing ranges, considering loading doses for drugs such as vancomycin to achieve target concentrations more rapidly, and prefe­rentially using prolonged b-lactam infusions to ensure adequate ƒT>MIC when hemodynamics and tissue perfusion are profoundly altered^{(5,6,38,40,42-44,46)}.

Special populations: cystic fibrosis and chronic suppurative lung disease

Children with cystic fibrosis (CF) present unique pharmacokinetic challenges due to increased drug clearance, larger volumes of distribution, and altered absorption of oral medications. For CF-associated pneumonia (particularly Pseudomonas aeruginosa, Burkholderia cepacia, or other multidrug-resistant pathogens), antipseudomonal b-lactams (piperacillin-tazobactam or meropenem) combined with inhaled or i.v. aminoglycosides are typically required^{(22,38,40,42-44,46)}. Dosing in CF requires escalation above standard pediatric recommendations: b-lactams often need 75-100 mg/kg/dose (or even higher) at more frequent intervals (every 6-8 hours rather than every 12 hours) to overcome enhanced clearance and maintain adequate ƒT>MIC⁽³⁾. Aminoglycosides similarly require higher mg/kg doses and more frequent intervals than standard pediatric dosing. Therapeutic drug monitoring is strongly recommended in CF children, particularly for aminoglycosides and vancomycin, due to unpredictable and often rapid clearance. Other chronic suppurative lung disease populations (bronchiectasis, chronic granulomatous disease) may similarly benefit from escalated dosing and TDM, where available.

Route of administration and i.v.-to-oral switch

Oral administration is preferred for mild to moderate disease in children who can tolerate oral intake and are hemodynamically stable, with high-dose oral amoxicillin being effective for many CAP cases^{(5,6,22,38,40,42-44,46)}. Intravenous therapy is indicated in children with severe disease, those unable to tolerate or absorb enteral medications, or when agents with only parenteral formulations are required^(2,3,30,44). An early i.v.-to-oral switch strategy – usually after 48-72 hours of clinical improvement, defervescence, and stable vital signs – is recommended to reduce hospitalization duration, catheter-related complications, and costs, while maintaining therapeutic efficacy. This strategy is safe and effective in children who can tolerate oral intake and are hemodynamically stable.

Duration of therapy: risk-stratified approach based on clinical stability

Emerging evidence from the 2025 guidelines conditionally recommends 3-5 days of antibiotic therapy for uncomplicated, non-severe CAP in children once clinical stability is achieved. Clinical stability is typically achieved within 48-72 hours of initiating appropriate treatment. This represents a significant shift from traditional 7-10-day courses and reflects accumulating pediatric evidence demonstrating noninferiority of shorter courses while reducing cumulative antibiotic exposure and selection pressure for resistance⁽⁴⁵⁾.

Extended durations (7-10 days or longer) remain indicated for:

• Severe disease (respiratory distress, hypoxemia, ICU admission).
• Pneumonia complicated by empyema, lung abscess, or necrotizing features.
• Infections caused by specific pathogens (Staphylococcus aureus, CA-MRSA, Mycoplasma pneumoniae).
• Children with immunodeficiency, chronic lung disease (cystic fibrosis, bronchiectasis), or poor clinical response after 48-72 hours of therapy⁽⁴⁵⁾.

Shortening therapy when clinically stable reduces cumulative antibiotic exposure, adverse events and selection pressure for resistance^{(6,36,39,45-47)}.

Systemic corticosteroids: indications and li­mi­ta­tions

For non-severe inpatient CAP: systemic corticosteroids are strongly recommended against (strong, low-quality evidence)^(1,4,5,6). There is no benefit to routine steroid use in hospitalized children with uncomplicated, non-severe pneumonia.

For severe inpatient CAP with respiratory compromise, systemic corticosteroids are now conditionally recommended (low-quality evidence) in selected cases meeting specific criteria:

• Documented hypoxemia requiring supplemental oxygen (SpO₂ <94% on room air).
• Severe respiratory distress with significant work of breathing (tachypnea, intercostal/subcostal retractions, grunting, nasal flaring).
• Early presentation (symptom onset
• Elevated inflammatory markers (elevated procalcitonin or CRP).
• ICU admission or complicated disease (empyema, abscess, necrotizing features).

Dosing (when indicated): dexamethasone 0.15 mg/kg daily (maximum 6 mg) p.o. or i.v. for up to 10 days or until hospital discharge, whichever comes first^(1,5,6).

Caution: corticosteroid use in children with influenza or COVID-19 requires careful risk-benefit assessment; steroids may be harmful in early uncomplicated viral infection, but may be justified in severe disease with respiratory failure. Clinical context and institutional guidelines should guide use.

Principles of antibiotic therapy in pediatric CAP, including bronchopneumonia: stewardship and rational use

Antimicrobial resistance among pediatric respiratory pathogens poses a growing threat. Resistance mechanisms include altered penicillin-binding proteins, beta-lactamase production, efflux pumps, and target site modification. These mechanisms necessitate careful antibiotic selection and dose optimization^(10-12). Antimicrobial stewardship programs promote rational antibiotic use by adhering to guidelines, monitoring resistance patterns and educating healthcare providers and caregivers. Antimicrobial stewardship is integral to pediatric respiratory care and constitutes a core component of the responsible management of CAP, including bronchopneumonia^{(4,10,11,12,36,37-40)}.

Antibiotics should be withheld when the clinical picture strongly supports a purely viral respiratory infection or when there is no evidence of bacterial superinfection in confirmed viral pneumonia^(4,16,34). Narrow-spectrum agents should be favored wherever feasible, and therapy should be individualized and de-escalated once microbiologic data are available and clinical improvement is evident^{(4-6,10,38,40,45,47)}. Biomarkers such as CRP and PCT can serve as adjuncts in supporting decisions regarding initiation, discontinuation and duration, although pediatric-specific evidence is still evolving⁽³⁶⁾.

Safety and adverse effects of antibiotics

Antibiotic therapy in children is generally safe but can be associated with adverse drug reactions, including gastrointestinal disturbances, hypersensitivity reactions and, more rarely, severe toxicity. Awareness of age-specific safety concerns is essential to minimize harm and support adherence to treatment^{(10,11,12,38,39,40,43)}.

Administering antibiotics in pediatric patients requires careful consideration of developmental pharmacokinetics and pharmacodynamics. Age-related differences in gastrointestinal absorption, body water and fat distribution, plasma protein binding, hepatic enzyme activity and renal clearance all influence drug exposure and toxicity risk. Although many adverse drug reactions resemble those seen in adults, their frequency, presentation and clinical impact may differ in children^(10,46,47).

Gastrointestinal adverse effects, particularly diarrhea, are among the most frequently reported antibio­tic-related adverse drug reactions (ADRs) in childhood. They occur more commonly with broad-spectrum agents such as amoxicillin-clavulanate and macrolides and are linked to disruption of the gut microbiome. In a minority of cases, this dysbiosis can predispose to Clostridioides difficile colitis, underscoring the importance of using the narrowest effective spectrum and limiting treatment duration^(10,43,47).

Hypersensitivity reactions represent a significant safety concern, especially with b-lactam antibiotics such as penicillin and cephalosporins. Type 1 IgE-mediated reactions may present with urticaria, angioedema, bronchospasm or anaphylaxis, whereas non-IgE-mediated reactions more often manifest as delayed maculopapular rashes. Mislabeling children as “penicillin allergic” after benign or non-immune rashes is common and can drive the use of broader-spectrum or less well-tolerated alternatives. Accurate assessment of suspected b-lactam allergy is therefore essential^(5,6,10).

Certain antibiotic classes carry specific developmental risks in children. Tetracyclines are generally avoi­ded in those under eight years of age because of dental enamel hypoplasia and permanent tooth discoloration. Fluoroquinolones, historically restricted due to animal data on cartilage toxicity (particularly levofloxacin), are increasingly recognized as reasonable and safe alternatives in pediatric CAP when b-lactam allergy (especially anaphylaxis) is documented or when resistant organisms require coverage. Levofloxacin is now recognized as the preferred oral agent for children as young as 6 months of age with penicillin anaphylaxis or severe allergy.

Clinical experience and pediatric trials have not demonstrated the joint toxicity predicted from animal studies, and fluoroquinolones are now acceptable first-line alternatives in selected pediatric populations rather than reserved agents⁽⁵⁾. However, routine use in young children without these indications remains unnecessary, and b-lactams remain preferred when tolerated. For such higher-risk classes, a prudent approach is to avoid routine use in young children, but accept carefully justified use in severe, resistant, or special infections when safer alternatives do not exist^{(5,6,10,16,17)}.

In this context, systematic clinical and laboratory monitoring should focus on the main antibiotic classes used in pediatric CAP and bronchopneumonia.

• β-lactams: monitor for hypersensitivity reactions and gastrointestinal intolerance.
• Macrolides: monitor for gastrointestinal adverse effects, QT interval prolongation and drug-drug interactions^(10,41).
• Aminoglycosides: monitor for nephrotoxicity and ototoxicity; TDM is strongly recommended^(10,40).
• Vancomycin: monitor for nephrotoxicity and infusion-related reactions; AUC-guided TDM is increasingly used to balance adequate exposure with reduced risk of renal injury⁽⁴³⁾.

Close monitoring is crucial in neonates, critically ill children and in those with preexisting renal or hepatic dysfunction, in whom altered drug hand­ling and limited physiological reserve substantially increase the risk of adverse outcomes. Integrating developmental pharmacology, structured safety monitoring and antimicrobial stewardship principles is essential to maximize the benefits and minimize the harms of antibiotic therapy in pediatric CAP and bronchopneumonia^{(4-6,10,36-38,40,46,47)}.

Strategies for preventing and effectively managing pediatric CAP

Prevention strategies. Vaccination, public health initiatives (education, hand hygiene, avoidance of tobacco smoke) and nutritional measures (breastfeeding, adequate nutrition) remain central to public health. Hib and pneumococcal conjugate vaccines, influenza vaccination, measles and pertussis immunization have all demonstrated substantial impact on pneumonia incidence and severity^(1-6,30,31).

Early detection and diagnosis. Routine health checkups and screening for risk factors are essential to identify high-risk children early^{(1,4,29,31,33)}. Standardized case definitions and consistent use of simple clinical signs, supported by pulse oximetry and chest radio­graphy when available, improve timely diagnosis and triage^(1-6,31-34).

Effective management strategies. Empirical antibiotic therapy should be based on local epidemiology and resistance patterns, with beta-lactams such as amoxicillin as first-line for typical bacterial pneumonia and macrolides considered for suspected atypical infections^{(10,15,19,23-25,41)}. Tailored treatment requires adjustment of antibiotic dosing based on age, weight, renal function and underlying comorbidities^{(5,6,30,36,42,47)}. In children with severe disease, sepsis or PICU admission, these adjustments often mean using higher mg/kg doses within recommended ranges and, for time-dependent b-lactams, considering prolonged infusions to maintain adequate concentrations in the face of altered distribution and clearance.

Supportive care (hydration, nutrition, oxygen ther­apy, respiratory support) is essential, especially in young infants and children with severe respiratory distress or hypoxemia^{(1,4-6,30,31,36,42,47)}. 

Monitoring and follow-up. Clinical monitoring and post-treatment follow-up should focus on the resolution of acute symptoms and the detection of complications. Children who required PICU admission or had marked respiratory compromise at presentation warrant closer follow-up for persistent symptoms and long-term respiratory sequelae such as bronchiectasis or impaired lung function^{(2,3,6,30,33)}. Preventing and effectively managing pediatric pneumonia thus requires an integrated strategy that combines prevention, early detection, individualized treatment informed by PK/PD principles, and ongoing stewardship^(1,10,11,12). 

Conclusions

Community acquired pneumonia, including bronchopneumonia, remains a leading cause of morbidity and mortality in children under 5 years of age, particularly in low- and middle-income countries, where socioeconomic disadvantage, malnutrition, incomplete immunization and environmental exposures amplify risk^{(1-6,16,17,30,31)}. Pediatric bronchopneumonia arises from a complex interplay of bacterial, viral and, in selected hosts, fungal pathogens, acting on a background of host vulnerability and structural inequities. Effective response, therefore, requires much more than antibiotic availability: it demands an integrated strategy spanning prevention, accurate diagnosis, rational pharmacotherapy, and health system strengthening. From a preventive standpoint, vaccination, promotion of breastfeeding, adequate nutrition and reduction of indoor air pollution and exposure to tobacco smoke remain fundamental^{(1,2,4-6,30,31)}. Diagnostic uncertainty, however, continues to drive empirical antibiotic use, and the review underscores the role of careful clinical assessment, imaging and microbiological and molecular diagnostics in refining etiology and supporting targeted therapy^{(1-6,14,31-35)}. Rational antimicrobial administration is central to the management of pediatric bronchopneumonia, being a significant focus of this review. Empirical treatment should target the most likely pathogens based on age, vaccination status, clinical severity and local epidemiology, with S. pneumoniae remaining the main bacterial target in children under five^(1,30,47). Consistent with national and international guidelines, oral amoxicillin is recommended as first-line therapy for most non-severe community-acquired pneumonia treated in outpatient settings, with macrolides reserved for school-aged children with suspected atypical infection or b-lactam allergy, and parenteral ampicillin, penicillin G or third-generation cephalosporins used in hospitalized children with moderate to severe disease. Appropriate dosing, route and duration must be grounded in pediatric pharmacokinetic and pharmacodynamic principles: age- and weight-adjusted regimens, attention to time- versus concentration-dependent killing, adequate exposure at the site of infection and, in selected situations, strategies such as prolonged b-lactam infusions or extended-interval aminoglycoside dosing^{(1,5,6,10,14,16,17,40,47)}.

The clinical challenge is to balance timely, effective treatment against the escalating threat of antimicrobial resistance. Misuse of antibiotics – whether through inappropriate selection, inadequate or excessive dosing, unnecessarily prolonged courses, or empirical use in clearly viral infections – undermines pharmacodynamic targets, increases the risk of treatment failure, and accelerates the emergence of resistant organisms. Repeated exposure to macrolides or cephalosporins may disrupt the microbiome and promote persistent carriage of resistant organisms, further reinforcing the need for stewardship^{(1,10-12,30,47)}.

This review also underscores the importance of supportive care and system-level interventions: implementation of pediatric antimicrobial stewardship programs, use of local antibiograms and adherence to guideline-based care. These have been shown to improve prescribing quality and reduce antimicrobial resistance. Strengthened infection prevention and control measures can reduce the incidence of nosocomial pneumonia and limit the spread of resistant pathogens. At the same time, caregiver and community education can improve adherence and reduce demand for unnecessary antibiotics.

As a narrative review, this work is limited by potential selection bias, heterogeneity of underlying studies and reliance on pre-COVID global burden estimates, which remain the most comprehensive data currently available. Nonetheless, by integrating etiological, epidemiological, clinical and pharmacological evidence, it aims to promote critical, evidence-based thinking about antibiotic use in pediatric bronchopneumonia in line with the WHO AWaRe framework and contemporary stewardship principles. Coordinated efforts to scale up prevention, refine diagnosis, apply PK/PD-informed antimicrobial regimens (including special populations such as children with cystic fibrosis, obesity, renal impairment, or severe malnutrition) and embed stewardship into routine pediatric practice are essential. If clinicians, institutions and policymakers align around these principles, the burden of pediatric CAP, including bronchopneumonia, can be substantially reduced, while preserving the effectiveness of existing antibiotics for future generations.

Autor corespondent: Ina Pogonea E-mail: ina.pogonea@usmf.md

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.