Bronkiektasis: Pendekatan Diagnosis dan Tatalaksana Eksaserbasi Berbasis Evidens

Pendahuluan

Bronkiektasis adalah kondisi respiratori kronik yang ditandai dengan dilatasi abnormal dan permanen dari bronkus, disertai dengan penebalan dinding bronkial akibat siklus inflamasi dan infeksi kronis. Kondisi ini mengakibatkan gangguan clearance mukus, kolonisasi bakteri kronik, dan eksaserbasi infeksi rekuren yang secara progresif merusak struktur paru. Meskipun dianggap sebagai “orphan disease” selama beberapa dekade, bronkiektasis kini mendapat perhatian lebih besar karena prevalensinya yang meningkat dan beban penyakit yang signifikan terhadap kualitas hidup pasien dan sistem kesehatan.

Definisi dan Epidemiologi

Definisi

Bronkiektasis didefinisikan sebagai dilatasi ireversibel dari pohon bronkial yang terlihat pada high-resolution computed tomography (HRCT) thoraks, dengan karakteristik:

• Diameter bronkus lebih besar dari arteri pulmonalis yang menyertainya (rasio broncho-arterial >1)
• Lack of bronchial tapering (bronkus tidak mengecil ke perifer)
• Visualisasi bronkus di perifer paru (dalam 1 cm dari pleura)

Epidemiologi

Prevalensi dan Insidensi:

• Prevalensi meningkat secara global: 53-566 per 100,000 populasi (bervariasi antar negara)
• Insidensi meningkat dengan usia: >1,100 per 100,000 pada usia >75 tahun
• Lebih tinggi pada wanita (rasio 1.5:1)
• Prevalensi meningkat dalam 2 dekade terakhir karena:
• Peningkatan deteksi (widespread use HRCT)
• Populasi aging
• Survival lebih lama dari underlying conditions
• Possible true increase dalam insidensi

Beban Penyakit:

• Penyebab signifikan morbiditas: eksaserbasi rekuren, hospitalisasi, penurunan kualitas hidup
• Mortalitas: 5-year survival rate 80-85%
• Biaya kesehatan substantial: hospitalisasi, antibiotik kronik, terapi suportif

Patofisiologi

Bronkiektasis berkembang melalui “vicious cycle hypothesis” (Cole’s vicious cycle):

Siklus Inflamasi-Infeksi:

1. Insult Awal:

• Infeksi severe (pneumonia, pertussis, TB)
• Obstruksi bronkial (foreign body, tumor)
• Aspiration
• Defek imunitas
• Kondisi genetik (cystic fibrosis, primary ciliary dyskinesia)

2. Kerusakan Mukosa dan Gangguan Clearance:

• Destruksi epitel ciliated
• Hipersekresi mukus
• Mukus menjadi kental dan sulit dibersihkan
• Stasis mukus dalam airways yang dilated

3. Kolonisasi Bakterial:

• Bakteri menempel pada mukus yang stagnant
• Biofilm formation (terutama P. aeruginosa)
• Kolonisasi kronik (presence bakteri tanpa symptoms)

4. Respons Inflamasi Berlebihan:

• Neutrophil recruitment masif
• Release proteases (elastase, metalloproteases)
• Oxidative stress
• Kerusakan structural airways progresif

5. Eksaserbasi Akut:

• Peningkatan bacterial load
• Symptoms worsen (batuk, sputum, dyspnea)
• Inflamasi meningkat

6. Perpetuasi Siklus:

• Kerusakan airways memfasilitasi infeksi lebih lanjut
• Airways dilated permanently
• Siklus terus berlanjut, causing progressive lung damage

Etiologi Bronkiektasis

Bronkiektasis dapat disebabkan oleh berbagai kondisi underlying:

Kategori Etiologi:

1. Post-Infectious (30-40%):

• Tuberkulosis (penyebab tersering globally, terutama negara endemic)
• Pneumonia severe childhood (measles, pertussis, adenovirus)
• Non-tuberculous mycobacteria (NTM)
• Necrotizing pneumonia (Staphylococcus aureus, Klebsiella)

2. Primary Ciliary Dyskinesia (PCD):

• Genetic disorder affecting ciliary function
• Kartagener’s syndrome (situs inversus + bronkiektasis + chronic sinusitis)

3. Immunodeficiency (5-10%):

• Common variable immunodeficiency (CVID)
• Selective IgA, IgG subclass deficiency
• HIV/AIDS

4. Cystic Fibrosis (CF):

• CFTR gene mutation
• Thick mucus, chronic infections
• Separate entity, managed differently

5. Allergic Bronchopulmonary Aspergillosis (ABPA):

• Hypersensitivity terhadap Aspergillus fumigatus
• Eosinophilia, elevated IgE
• Central bronchiectasis pattern

6. Connective Tissue Diseases:

• Rheumatoid arthritis
• Sjögren’s syndrome
• Inflammatory bowel disease (ulcerative colitis)

7. Aspiration:

• Recurrent aspiration (dysphagia, GERD, neurologic disorders)

8. Obstructive Bronchial Lesions:

• Foreign body
• Tumor (endobronchial atau extrinsic compression)
• Lymphadenopathy

9. Alpha-1 Antitrypsin Deficiency

10. Idiopathic (25-50%):

• No identifiable cause meskipun extensive workup
• Kemungkinan genetic susceptibility atau unrecognized mild immunodeficiency

Mikrobiologi: Patogen Penyebab Infeksi

Bronkiektasis ditandai dengan kolonisasi bakteri kronik dan eksaserbasi infeksi akut. Spektrum patogen bervariasi berdasarkan severity penyakit, riwayat antibiotik, dan underlying etiology.

Patogen Bakterial Utama:

1. Haemophilus influenzae

• Patogen tersering pada bronkiektasis (30-50% pasien)
• Non-typeable strains (tidak tercakup vaksin Hib)
• Karakteristik:
• Gram-negative coccobacillus
• Kolonisasi early disease
• Sering pada bronkiektasis mild-moderate
• Manifestasi:
• Eksaserbasi dengan sputum purulen
• Umumnya less severe dibanding Pseudomonas
• Resistensi:
• Beta-lactamase production (20-30% strain)
• Amoxicillin resistance meningkat

2. Pseudomonas aeruginosa

• 10-30% bronkiektasis patients, meningkat dengan severity disease
• Gram-negative rod
• Karakteristik:
• Biofilm formation: Membuat eradikasi sulit
• Mucoid strains: Produksi alginate polysaccharide
• Multidrug resistance common
• Associated dengan:
• Severe disease (FEV1 lebih rendah, eksaserbasi lebih frequent)
• Worse prognosis: Increased hospitalization, mortality
• Previous antibiotic exposure (terutama fluoroquinolones, beta-lactams)
• Structural lung damage extensive
• Transmission: Dapat acquired dari environment (water sources) atau person-to-person
• Management challenge:
• Sulit eradikasi sekali established
• Memerlukan prolonged antibiotic therapy
• Risk resistensi dengan repeated exposures

3. Streptococcus pneumoniae (Pneumococcus)

• 10-15% bronkiektasis patients
• Gram-positive diplococcus
• Karakteristik:
• Lebih sering pada eksaserbasi akut daripada kolonisasi kronik
• Dapat menyebabkan pneumonia superimposed
• Vaksinasi pneumococcal penting untuk prevention

4. Moraxella catarrhalis

• 5-10% patients
• Gram-negative diplococcus
• Karakteristik:
• Sering pada elderly dan COPD overlap
• >95% strains produce beta-lactamase
• Amoxicillin resistance tinggi
• Umumnya mild infections
• Treatment: Memerlukan beta-lactamase inhibitor atau alternative antibiotik

5. Staphylococcus aureus

• 5-15% patients
• Gram-positive cocci
• MSSA (Methicillin-Sensitive S. aureus):
• Dapat colonize dan cause eksaserbasi
• MRSA (Methicillin-Resistant S. aureus):
• Risk factors: Previous hospitalization, healthcare exposure, IV antibiotics
• Associated dengan worse outcomes
• Memerlukan antibiotik spesifik (vancomycin, linezolid)
• More common pada CF-related bronchiectasis

Patogen Lain:

Gram-Negative Rods:

• Klebsiella pneumoniae
• Escherichia coli
• Enterobacter species
• Stenotrophomonas maltophilia (intrinsically multidrug-resistant)
• Achromobacter species

Anaerobes:

• Terkait aspiration
• Mixed infections

Non-Tuberculous Mycobacteria (NTM)

Insidensi meningkat secara global dalam 2 dekade terakhir, terutama di negara developed.

Epidemiologi:

Prevalensi:

• 5-20% bronkiektasis patients (bervariasi geografis)
• Increasing incidence: 2-fold hingga 4-fold increase dalam 15-20 tahun terakhir
• Reasons untuk increase:
• Improved diagnostic techniques (PCR, culture methods)
• Aging population (elderly lebih susceptible)
• Greater awareness dan testing
• Possible environmental factors (water exposure)
• Underlying immunosuppression (biologics, steroids)

Species Utama:

Mycobacterium avium Complex (MAC):

• Paling sering (70-80% NTM infections)
• Termasuk M. avium dan M. intracellulare
• “Lady Windermere Syndrome”: MAC infection pada elderly women, non-smokers, dengan body habitus kecil, affecting middle lobe/lingula

Mycobacterium abscessus Complex:

• Rapidly growing mycobacteria (RGM)
• 15-20% NTM infections pada bronkiektasis
• Highly drug-resistant
• Associated dengan worse prognosis
• More common pada CF, previous antibiotic exposure

Species Lain:

• M. kansasii, M. xenopi, M. malmoense

Manifestasi Klinis NTM:

Gejala:

• Chronic productive cough (>3 bulan)
• Fatigue, weight loss, night sweats
• Hemoptysis
• Progressive dyspnea
• Symptoms overlap dengan bronkiektasis sendiri

Imaging:

• Nodular bronchiectasis pattern (small nodules + bronkiektasis)
• “Tree-in-bud” appearance
• Cavitation (terutama M. abscessus, M. kansasii)
• Middle lobe/lingula involvement (M. avium)

Diagnosis NTM (American Thoracic Society/IDSA Criteria):

Memerlukan ALL dari:

1. Clinical Criteria:

• Pulmonary symptoms, nodular/cavitary opacities, atau multifocal bronchiectasis pada HRCT

2. Microbiologic Criteria (ONE dari):

• ≥2 positive sputum cultures dengan interval waktu berbeda
• ≥1 positive bronchial wash/lavage culture
• Transbronchial/lung biopsy dengan mycobacterial histopathology dan positive culture

3. Exclusion dari other diagnoses

Treatment NTM:

MAC:

• Macrolide-based regimen: Azithromycin atau clarithromycin
• Plus ethambutol
• Plus rifampin
• Duration: Minimal 12 bulan setelah culture conversion (sputum negative)
• Tambahan amikacin atau streptomycin untuk cavitary/severe disease

M. abscessus:

• Extremely difficult to treat
• Multi-drug regimen:
• Intensive phase (IV): Amikacin + cefoxitin atau imipenem + macrolide (months)
• Continuation phase (oral): Macrolide-based regimen
• Duration: ≥12-18 bulan post-culture conversion
• Cure rates low (50-60%)

Monitoring:

• Monthly sputum cultures during treatment
• Monitor for drug toxicity (hearing, vision, liver, kidney)
• HRCT for radiographic response

Fungi:

Aspergillus Species:

• ABPA (allergic response)
• Chronic pulmonary aspergillosis (cavity colonization)
• Invasive aspergillosis (immunocompromised)

Manifestasi Klinis

Gejala Kronik:

1. Batuk Produktif:

• Hallmark symptom
• Daily sputum production (sering copious, >30 mL/hari)
• Purulent atau mucopurulent
• Worse di pagi hari (accumulated secretions overnight)

2. Dyspnea:

• Progressive dengan aktivitas
• Berhubungan dengan severity disease

3. Hemoptysis:

• 50-70% patients at some point
• Range dari blood-streaked sputum hingga massive hemoptysis
• Caused by:
• Friable, inflamed bronchial mucosa
• Hypertrophied bronchial arteries
• Massive hemoptysis (>200 mL/24 jam): Medical emergency

4. Chest Pain:

• Pleuritic pain saat eksaserbasi
• Musculoskeletal pain dari coughing chronik

5. Fatigue dan Malaise:

• Chronic inflammation
• Poor sleep quality (cough nocturnal)

6. Wheeze:

• Airflow obstruction
• Bronchial secretions

7. Sinusitis Kronik:

• Upper airway symptoms common
• Especially pada PCD, CF, ABPA

Tanda Fisik:

Inspeksi:

• Clubbing (10-30%) – severe disease
• Cachexia – advanced disease

Auskultasi:

• Crackles (ronki): Coarse, inspiratory (affected areas)
• Wheeze: Airflow obstruction
• Squeaks: Small airway disease

Advanced Disease:

• Cyanosis (chronic hypoxia)
• Cor pulmonale (signs right heart failure)

Eksaserbasi Akut:

Definisi: Acute deterioration memerlukan treatment change

Gejala Eksaserbasi:

• Peningkatan batuk
• Increased sputum volume (>50% dari baseline)
• Change sputum purulence (warna lebih gelap, lebih thick)
• Increased dyspnea
• Fatigue atau malaise meningkat
• Hemoptysis (baru atau meningkat)
• Fever (tidak selalu ada)

Severity Grading Eksaserbasi:

Mild:

• Symptoms meningkat namun tolerable
• Tidak mengganggu daily activities significantly
• Manageable outpatient dengan oral antibiotik

Moderate:

• Symptoms significant
• Mengganggu daily activities
• May require outpatient treatment intensified atau short hospitalization

Severe:

• Marked deterioration
• Systemic symptoms: High fever, significant dyspnea, hemodynamic instability
• Hypoxemia (SpO2 <90%)
• Requires hospitalization, possibly ICU
• IV antibiotics

Diagnosis

Diagnosis Bronkiektasis:

A. High-Resolution Computed Tomography (HRCT) Thoraks

Gold standard untuk diagnosis bronkiektasis.

Findings:

• Broncho-arterial ratio >1: Bronkus lebih besar dari arteri yang menyertainya
• Lack of tapering: Bronkus tidak mengecil ke arah perifer
• Peripheral bronchi visible: Terlihat dalam 1 cm dari pleura
• “Signet ring sign”: Cross-section bronkus dan arteri menyerupai signet ring
• “Tram track sign”: Parallel lines dari thickened bronchial walls

Patterns:

• Cylindrical: Uniform dilatasi (most common)
• Varicose: Irregular dilatasi (beaded appearance)
• Cystic/saccular: Severe dilatasi dengan cystic spaces

Distribution:

• Focal vs. diffuse
• Lobar distribution: Clues untuk etiology
• Upper lobe: TB, ABPA, CF
• Middle lobe/lingula: MAC, aspiration
• Lower lobe: Aspiration, idiopathic

B. Chest X-Ray

Tidak cukup sensitif untuk diagnosis, namun dapat menunjukkan:

• Tram tracks
• Ring shadows
• Crowding airways
• Atelectasis, consolidation

Indikasi CXR pada bronkiektasis established:

• Eksaserbasi severe atau suspek pneumonia superimposed
• Hemoptysis significant
• Decline fungsi unexplained
• Monitor complications (lung abscess, empyema)

Pemeriksaan untuk Etiologi:

Initial Workup:

• Serum immunoglobulins (IgG, IgA, IgM, IgG subclasses)
• ABPA screening: Total IgE, Aspergillus specific IgE/IgG, eosinophils
• Alpha-1 antitrypsin level
• Rheumatoid factor, anti-CCP (jika arthritis symptoms)
• Sweat chloride test atau CFTR genetic testing (jika suspek CF)

Extended Workup (jika indicated):

• Ciliary function testing: Nasal nitric oxide, high-speed video microscopy (PCD)
• HIV testing
• Autoimmune panel (ANA, RF, anti-Ro, anti-La)

Mikrobiologi: Kultur Sputum

Peran Krusial Kultur Sputum:

Sputum culture DIPERLUKAN pada setiap eksaserbasi untuk:

1. Identifikasi Patogen:

• Guide antibiotic selection
• Detect emerging resistant organisms
• Identify new pathogens (Pseudomonas, NTM)

2. Susceptibility Testing:

• Antibiotic sensitivity pattern
• Detect multidrug resistance
• Guide definitive therapy

3. Monitor Kolonisasi:

• Track chronic colonizing organisms
• Detect Pseudomonas acquisition (prognostic significance)
• Detect NTM

4. Epidemiological Surveillance:

• Track resistance patterns locally

Prosedur Kultur Sputum:

Specimen Collection:

• Spontaneous sputum (most common)
• Deep cough, early morning preferred
• Rinse mouth dengan air (remove oral contaminants)
• Induced sputum: Nebulized hypertonic saline jika tidak dapat ekspektorasi spontan
• Bronchoscopy dengan BAL: Jika unable sputum, atau suspek specific patogen (NTM, Aspergillus)

Quality Criteria:

• >25 neutrophils dan <10 epithelial cells per low-power field (Gram stain)
• Ensures lower respiratory tract origin

Laboratory Processing:

Standard Culture:

• Gram stain: Initial morphology
• Routine bacterial culture: Aerobic dan anaerobic (jika indicated)
• Susceptibility testing: Minimum inhibitory concentration (MIC)

Extended Cultures (jika indicated):

• Mycobacterial culture:
• Acid-fast bacilli (AFB) smear
• Culture (solid media 6-8 weeks, liquid media 2-4 weeks)
• Indikasi: Suspek TB atau NTM, chronic symptoms, compatible imaging
• Frequency: ≥3 separate sputum samples untuk NTM diagnosis
• Fungal culture:
• Aspergillus species
• Endemic fungi (jika relevant geography)

Molecular Testing:

• PCR/NAAT: Rapid detection Pseudomonas, Mycobacterium, Aspergillus
• 16S rRNA sequencing: Identify unusual organisms

Interpretation:

Kolonisasi vs. Infection:

• Kolonisasi: Organism present tanpa clinical deterioration
• Infection/Eksaserbasi: Organism + symptoms worsening

Culture Results dan Management:

• Pathogen identified: Direct therapy based on susceptibilities
• No growth: Consider viral, atypical organisms, atau inadequate specimen
• Polimicrobial: Common pada bronkiektasis; treat predominant pathogen atau multiple

NTM Considerations:

• Single positive culture: Monitor, repeat cultures
• ≥2 positive cultures: Meet diagnostic criteria + clinical/radiographic correlation → consider treatment

Pemeriksaan Lain:

Spirometry:

• Assess obstructive pattern (FEV1/FVC <0.7)
• Monitor decline fungsi
• Severity assessment

Arterial Blood Gas atau Pulse Oximetry:

• Assess gas exchange
• Hypoxemia pada severe disease

6-Minute Walk Test:

• Functional capacity
• Desaturation dengan exercise

Inflammatory Markers:

• CRP, ESR: Elevated selama eksaserbasi

Sputum Inflammatory Markers (Research):

• Neutrophil elastase, IL-8

Tatalaksana Eksaserbasi Akut

Manajemen eksaserbasi bronkiektasis memerlukan pendekatan individualized berdasarkan severity eksaserbasi, riwayat kolonisasi patogen (terutama P. aeruginosa), dan kultur sputum results.

Prinsip Umum:

1. Kultur sputum sebelum starting antibiotik (jika possible)
2. Empirical antibiotic therapy immediately jika severely ill
3. Adjust therapy berdasarkan kultur results dan clinical response
4. Airway clearance intensified
5. Supportive care

Pemilihan Terapi Antibiotik

A. Eksaserbasi Mild-Moderate TANPA Riwayat Pseudomonas aeruginosa

Karakteristik:

• No prior P. aeruginosa isolation dari sputum cultures
• Mild-moderate symptoms: Increased cough/sputum, tolerable dyspnea
• Dapat dimanage outpatient
• Stable vital signs, no hypoxia

Patogen yang Kemungkinan:

• H. influenzae (tersering)
• S. pneumoniae
• M. catarrhalis
• S. aureus (MSSA)

Antibiotik Pilihan Pertama:

Amoxicillin-Clavulanate (Co-amoxiclav):

• Dosis:
• 875 mg/125 mg twice daily (standard)
• Atau 2000 mg/125 mg twice daily (extended-release, untuk severe atau beta-lactamase producers)
• Durasi: 7-10 hari (some guidelines 14 hari untuk severe)
• Rasional:
• Excellent coverage: H. influenzae (including beta-lactamase producing), M. catarrhalis, S. pneumoniae, S. aureus (MSSA)
• Clavulanate overcomes beta-lactamase resistance
• First-line choice dalam most guidelines (ERS, BTS)
• High success rate (70-85% clinical improvement)
• Efek samping: Diare (10-25%), nausea
• Mitigasi: Minum dengan makanan, consider probiotics

Alternative jika Poor Response atau Intolerance:

Doxycycline:

• Dosis: 100 mg twice daily × 7-10 hari
• Coverage: H. influenzae, M. catarrhalis, S. pneumoniae, atypicals
• Considerations:
• Beta-lactamase resistance tidak issue
• Good penetration respiratory tract
• Cost-effective
• Limitations: S. aureus coverage variable
• Kontraindikasi: Kehamilan, laktasi, anak <8 tahun

Trimethoprim-Sulfamethoxazole (Co-trimoxazole):

• Dosis: 160/800 mg (DS) twice daily × 7-10 hari
• Coverage: H. influenzae, M. catarrhalis, S. aureus (including some MRSA strains)
• Limitations:
• S. pneumoniae resistance increasing (>30% di beberapa area)
• Not first-line
• Efek samping: Rash, GI upset, hyperkalemia

Alergi Beta-Laktam (Non-Anafilaksis):

Cephalosporins (Second/Third Generation):

• Cefuroxime: 500 mg twice daily × 7-10 hari
• Cefpodoxime: 200 mg twice daily × 7-10 hari
• Cefdinir: 300 mg twice daily × 7-10 hari
• Coverage: H. influenzae, M. catarrhalis, S. pneumoniae

Alergi Beta-Laktam (Anafilaksis):

Respiratory Fluoroquinolones (RESERVED, see below):

• Levofloxacin: 500-750 mg once daily × 7-10 hari
• Moxifloxacin: 400 mg once daily × 7-10 hari

Atau:

• Doxycycline (if tolerated)
• Azithromycin: 500 mg once daily × 5 hari (resistance concerns untuk H. influenzae dan S. pneumoniae)

B. Eksaserbasi Mild-Moderate DENGAN Suspek atau Confirmed Pseudomonas aeruginosa

Karakteristik:

• Prior isolation P. aeruginosa dari sputum (dalam 12 bulan)
• Atau suspek P. aeruginosa:
• Severe structural damage
• Frequent eksaserbasi (≥3/tahun)
• Recent hospitalization
• Recent broad-spectrum antibiotics
• Chronic macrolide atau inhaled antibiotik use
• Mild-moderate symptoms namun outpatient management possible
• No sepsis atau respiratory failure

Antibiotik Pilihan:

Fluoroquinolones dengan Anti-Pseudomonal Activity:

Ciprofloxacin (Preferred):

• Dosis oral:
• 500-750 mg twice daily × 14 hari
• Higher dose (750 mg BID) untuk severe disease atau known P. aeruginosa
• Rasional:
• Excellent anti-Pseudomonas activity
• High bioavailability (oral ≈ IV)
• Good penetration respiratory secretions
• Standard choice untuk outpatient Pseudomonas treatment
• Durasi: 14 hari (longer than non-Pseudomonas infections)
• Necessary untuk prevent relapse
• Biofilm eradication difficult
• Considerations:
• Monitor for resistance: P. aeruginosa dapat develop resistance during therapy
• Repeat sputum culture post-treatment untuk assess eradication

Levofloxacin:

• Dosis: 750 mg once daily × 14 hari
• Rasional:
• Anti-Pseudomonas activity (less potent than ciprofloxacin)
• Once-daily dosing (improved compliance)
• Broader spectrum (better S. pneumoniae coverage)
• Preferred jika: Co-infection S. pneumoniae suspected

Concerns dengan Fluoroquinolones:

FDA Black Box Warnings:

• Tendon rupture (especially Achilles tendon)
• Risk factors: Age >60, corticosteroids, renal failure
• Advise stop immediately jika tendon pain
• Peripheral neuropathy (permanent)
• CNS effects: Seizures, confusion, delirium
• Aortic aneurysm/dissection (elderly, hypertension, connective tissue disorders)
• QT prolongation
• Dysglycemia (hypo- atau hyperglycemia)

Kontraindikasi:

• Myasthenia gravis (exacerbation risk)
• History tendon disorders
• QT prolongation atau medications prolonging QT
• Pregnancy, breastfeeding
• Children (cartilage damage concerns) – use only jika no alternatives

Drug Interactions:

• Antacids, calcium, iron, zinc: Chelation (space 2 jam)
• Warfarin: Increased INR
• Theophylline: Increased levels
• NSAIDs: Increased seizure risk

Alternative jika Fluoroquinolone Contraindicated atau Resistance:

IV Antibiotics (Hospitalization atau Home IV Therapy):

• Ceftazidime: 2 g IV every 8 jam × 14 hari
• Cefepime: 2 g IV every 8-12 jam × 14 hari
• Piperacillin-tazobactam: 4.5 g IV every 6 jam × 14 hari
• Meropenem: 1-2 g IV every 8 jam × 14 hari (reserve untuk MDR)
• Aztreonam: 2 g IV every 8 jam (beta-lactam allergy)

Combination Therapy (Severe Pseudomonas Infections):

• Beta-lactam + aminoglycoside atau beta-lactam + fluoroquinolone
• Rationale: Synergy, prevent resistance
• Example: Ceftazidime + tobramycin

Inhaled Antibiotics (Adjunct):

• Tobramycin nebulizer solution: 300 mg twice daily
• Colistin nebulizer: 1-2 million units twice daily
• Can add to oral/IV therapy untuk increase sputum concentrations

C. Eksaserbasi Severe

Karakteristik:

• Severe symptoms: Marked dyspnea, high fever, hemoptysis
• Systemic toxicity: Sepsis, hemodynamic instability
• Hypoxemia: SpO2 <90%, PaO2 <60 mmHg
• Pneumonia superimposed: Infiltrat baru pada CXR
• Requires hospitalization, possibly ICU

Management:

1. Hospitalization:

• ICU admission jika respiratory failure, septic shock, massive hemoptysis

2. IV Antibiotics:

Empirical Broad-Spectrum:

Jika NO Prior P. aeruginosa:

• Ceftriaxone: 1-2 g IV once daily
• Atau Cefotaxime: 1-2 g IV every 8 jam
• Atau Ampicillin-sulbactam: 3 g IV every 6 jam
• Plus optional macrolide jika atypical coverage needed

Jika Prior P. aeruginosa atau HIGH RISK:

• Anti-pseudomonal beta-lactam:
• Piperacillin-tazobactam: 4.5 g IV every 6 jam
• Ceftazidime: 2 g IV every 8 jam
• Cefepime: 2 g IV every 8 jam
• Meropenem atau imipenem: Reserved untuk MDR, carbapenem-resistant organisms
• Consider combination:
• Plus aminoglycoside (tobramycin 5-7 mg/kg IV once daily)
• Atau plus fluoroquinolone (IV ciprofloxacin 400 mg every 8-12 jam)

Jika Suspek MRSA:

• Add vancomycin: 15-20 mg/kg IV every 8-12 jam (target trough 15-20 mcg/mL)
• Atau linezolid: 600 mg IV/PO every 12 jam

3. Supportive Care:

• Oxygen therapy: Target SpO2 ≥92%
• IV fluids: Hydration
• Bronchodilators: Albuterol, ipratropium
• Corticosteroids: Consider short course (prednisone 30-40 mg × 7-14 hari) jika bronchospasm significant (controversial, not routine)
• Airway clearance intensified: Physiotherapy, oscillatory devices

4. De-escalation:

• Switch to oral antibiotics once clinically stable (48-72 jam apyrexia, improved symptoms)
• Tailor based on culture results dan susceptibilities
• Complete 14-day course total (IV + oral)

5. Complications Management:

• Massive hemoptysis: Bronchial artery embolization, surgery jika refractory
• Pneumothorax: Chest tube
• Empyema: Drainage, prolonged antibiotics
• Respiratory failure: Mechanical ventilation

Manajemen Berbasis Riwayat Patogen:

Summary Algoritma:

Mild-Moderate Eksaserbasi:

TANPA Prior P. aeruginosa:

1. First-line: Amoxicillin-clavulanate 875/125 mg BID × 7-10 hari
2. Alternative: Doxycycline, co-trimoxazole, cephalosporin (alergi)
3. Levofloxacin atau moxifloxacin: Reserved untuk poor response atau beta-lactam allergy

DENGAN Prior P. aeruginosa:

1. First-line: Ciprofloxacin 500-750 mg BID × 14 hari
2. Alternative: Levofloxacin 750 mg once daily × 14 hari
3. Jika resistance atau contraindication: IV therapy (hospitalization atau home IV)

Severe Eksaserbasi:

• Hospitalization, IV antibiotics, supportive care
• Broad-spectrum coverage including anti-pseudomonal agent
• De-escalate based on cultures dan clinical improvement

Monitoring Response:

Clinical Assessment (48-72 Jam):

• Improvement expected: Reduced cough, sputum volume, dyspnea
• Apyrexia within 72 jam
• Improved exercise tolerance

Jika NO Improvement:

• Review kultur results: Switch antibiotik based on susceptibilities
• Consider resistant organism atau alternative diagnosis
• Imaging: CXR atau HRCT untuk rule out complications (pneumonia, abscess, empyema)
• Consider hospitalization untuk IV antibiotics

Post-Treatment:

• Repeat sputum culture 4-6 minggu post-eksaserbasi (especially jika P. aeruginosa treated)
• Assess for eradication vs. persistent kolonisasi

Chest Radiograph (CXR):

Indikasi untuk CXR pada Bronkiektasis Eksaserbasi:

1. Severe Symptoms:

• Marked dyspnea atau respiratory distress
• High fever (>39°C) persistent
• Hemoptysis significant (>30 mL)
• Pleuritic chest pain

2. Suspek Pneumonia:

• Focal consolidation pada physical exam (dullness, bronchial breathing, crackles localized)
• Lack of response terhadap standard antibiotik untuk bronkiektasis eksaserbasi

3. Complications:

• Pneumothorax suspected (sudden dyspnea, chest pain, decreased breath sounds)
• Empyema (persistent fever, chest pain, toxic appearance)
• Lung abscess (prolonged fever, foul-smelling sputum)

4. First Severe Eksaserbasi:

• Establish baseline
• Rule out alternative diagnoses

5. Hospitalization:

• Routine untuk severe eksaserbasi requiring admission

Findings yang Mungkin:

• New infiltrat: Superimposed pneumonia
• Atelectasis: Mucus plugging
• Pleural effusion: Parapneumonic atau empyema
• Cavitation: Abscess
• Pneumothorax
• Worsening bronchiectasis changes

TIDAK Rutin Diperlukan:

• Mild eksaserbasi yang respond well terapi oral
• Typical symptoms tanpa red flags
• CXR recente (dalam 6-12 bulan) tanpa change klinis significant

Tatalaksana Jangka Panjang (Stable State)

Tujuan:

1. Reduce eksaserbasi frequency dan severity
2. Preserve lung function
3. Improve quality of life
4. Prevent complications

Komponen Utama:

A. Airway Clearance Techniques

Cornerstone therapy – mengurangi mucus stasis dan bacterial load.

Teknik:

• Chest physiotherapy: Postural drainage, percussion, vibration
• Positive expiratory pressure (PEP) devices
• Oscillatory PEP devices: Flutter valve, Acapella
• High-frequency chest wall oscillation (HFCWO) vest
• Autogenic drainage

Frequency: Daily, 1-2 kali sehari, increased selama eksaserbasi

B. Mucoactive Agents

Hypertonic Saline (3-7%):

• Nebulized twice daily
• Mechanism: Hydrates mucus, improves clearance
• Evidence: Reduces eksaserbasi

Mannitol Dry Powder:

• Inhaled osmotic agent
• Alternative untuk hypertonic saline

N-Acetylcysteine:

• Evidence mixed, not routinely recommended

C. Bronchodilators

Jika Airflow Obstruction atau Bronchial Hyperreactivity:

• Beta-2 agonists: Albuterol/salbutamol
• Anticholinergics: Ipratropium, tiotropium
• Long-acting bronchodilators: Jika COPD overlap

D. Anti-Inflammatory Therapy

Inhaled Corticosteroids:

• NOT routinely recommended untuk non-CF bronkiektasis
• Consider jika: COPD overlap, asthma, ABPA
• Concerns: Increased infection risk (especially NTM)

Macrolide Antibiotics (Long-Term, Low-Dose):

• Azithromycin: 250-500 mg three times weekly atau 250 mg daily
• Mechanism: Anti-inflammatory (immunomodulatory), anti-biofilm
• Indications: ≥3 eksaserbasi per tahun
• Benefits:
• Reduce eksaserbasi rate 40-50%
• Improve quality of life
• Duration: Minimum 6-12 bulan
• Monitoring:
• Baseline: ECG (QT interval), NTM sputum culture, hearing test
• Periodic: Repeat NTM cultures (risk selecting resistant NTM, especially MAC)
• Liver function tests
• Contraindications:
• NTM infection (risk resistance)
• QT prolongation
• Hearing impairment

E. Long-Term Antibiotics

Inhaled Antibiotics:

Indications:

• Chronic P. aeruginosa infection (≥2 positive cultures, ≥3 months apart dalam 1 tahun)
• Frequent eksaserbasi (≥3/tahun) meskipun optimal airway clearance

Agents:

• Tobramycin inhalation solution: 300 mg twice daily (28 days on / 28 days off cycles)
• Colistimethate sodium (Colistin): 1-2 million units twice daily
• Aztreonam lysine: 75 mg three times daily

Benefits:

• Reduce bacterial density dalam sputum
• Decrease eksaserbasi frequency
• Preserve lung function

Monitoring:

• Sputum cultures: Quarterly untuk assess bacterial suppression dan resistance
• Audiometry: Aminoglycosides (tobramycin) – hearing loss risk
• Spirometry: Monitor lung function
• Bronchospasm: Pre-medicate dengan bronchodilator

Rotating Antibiotics:

• Alternate antibiotics monthly untuk prevent resistance

Oral Antibiotics (Rotating):

• Less common strategy
• Rotating regimens: E.g., amoxicillin-clavulanate 2 weeks/month
• Evidence limited compared dengan inhaled

F. Manajemen Komorbiditas

GERD:

• PPI therapy: Reduce aspiration risk

Chronic Rhinosinusitis:

• Nasal saline irrigation
• Intranasal corticosteroids
• Treat sinusitis aggressively

Immunodeficiency:

• Immunoglobulin replacement therapy (IVIG atau SCIG) jika CVID atau severe IgG deficiency

ABPA:

• Corticosteroids: Prednisone 0.5 mg/kg
• Itraconazole: Antifungal therapy

G. Vaksinasi

Pneumococcal Vaccines:

• PCV13 atau PCV20 + PPSV23 (jika applicable)

Influenza Vaccine:

• Annual

COVID-19 Vaccine:

• Primary series + boosters

Pertussis (Tdap):

• Booster setiap 10 tahun

H. Nutrisional Support

Adequate Protein dan Caloric Intake:

• Combat weight loss, muscle wasting

Vitamin D Supplementation:

• Jika deficient

I. Pulmonary Rehabilitation

Exercise Training:

• Improve exercise capacity, muscle strength
• Reduce dyspnea
• Enhance quality of life

J. Oxygen Therapy

Jika Chronic Hypoxemia:

• Long-term oxygen therapy (PaO2 <55 mmHg atau SpO2 <88%)

K. Surgical Options (Selected Cases)

Indications:

• Localized disease (1-2 lobes) dengan frequent infections despite optimal medical therapy
• Massive hemoptysis refractory medical management
• Lung abscess atau empyema not resolving

Procedures:

• Lobectomy atau segmentectomy: Resect affected lobe
• Bronchial artery embolization: Hemoptysis management

L. Lung Transplantation

Consideration jika:

• End-stage disease dengan respiratory failure
• Frequent hospitalization
• FEV1 <30% predicted
• Hypoxemia atau hypercapnia
• Pulmonary hypertension

Prognosis

Variable berdasarkan:

• Underlying etiology
• Severity disease (extent anatomical damage)
• P. aeruginosa chronic infection: Worse prognosis
• Frequency eksaserbasi: Accelerate decline
• Comorbidities

Predictors Poor Prognosis:

• Age >70 tahun
• P. aeruginosa kolonisasi
• NTM infection (especially M. abscessus)
• Severe airflow obstruction (FEV1 <30%)
• Radiologic severity (≥5 lobes involved, cystic changes)
• Frequent eksaserbasi (≥3/tahun)
• Underweight (BMI <18.5)

Mortality:

• 5-year survival: 80-85%
• 10-year survival: 60-70%
• Leading causes of death: Respiratory failure, pneumonia, sepsis, massive hemoptysis

Kesimpulan

Bronkiektasis adalah kondisi kronik kompleks yang memerlukan manajemen komprehensif dan individualized. Patogen bakterial utama meliputi Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Moraxella catarrhalis, dan Staphylococcus aureus, dengan insidensi non-tuberculous mycobacteria yang meningkat secara global memerlukan awareness dan testing yang lebih tinggi.

Kultur sputum pada setiap eksaserbasi adalah esensial untuk guide antibiotic therapy dan monitor resistensi. Pemilihan antibiotik harus berdasarkan severity eksaserbasi dan terutama riwayat isolasi P. aeruginosa sebelumnya:

• Eksaserbasi mild-moderate tanpa P. aeruginosa: Amoxicillin-clavulanate 875/125 mg BID × 7-10 hari (first-line), dengan levofloxacin sebagai alternative untuk poor response atau alergi beta-laktam
• Eksaserbasi mild-moderate dengan P. aeruginosa: Ciprofloxacin 500-750 mg BID × 14 hari atau levofloxacin 750 mg once daily × 14 hari
• Eksaserbasi severe: Hospitalisasi dengan IV antibiotics broad-spectrum

Chest radiograph diindikasikan untuk gejala severe atau kecurigaan pneumonia superimposed, namun tidak rutin untuk eksaserbasi ringan yang respond well.

Manajemen jangka panjang fokus pada airway clearance techniques, manajemen patogen kronik (inhaled antibiotics untuk P. aeruginosa, long-term macrolides untuk frequent exacerbators), vaksinasi, dan pulmonary rehabilitation untuk optimize quality of life dan memperlambat disease progression. Pendekatan multidisiplin yang proaktif dapat significantly improve outcomes dan reduce disease burden pada pasien dengan bronkiektasis.

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