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Bronchiectasis in adults: Treatment of acute exacerbations and advanced disease

Bronchiectasis in adults: Treatment of acute exacerbations and advanced disease
Author:
Alan F Barker, MD
Section Editor:
James K Stoller, MD, MS
Deputy Editor:
Paul Dieffenbach, MD
Literature review current through: Dec 2022. | This topic last updated: Oct 19, 2022.

INTRODUCTION — Bronchiectasis is characterized by pathologic airway dilatation and bronchial wall thickening, which manifests clinically as chronic cough and daily viscid sputum production. Multiple conditions are associated with the development of bronchiectasis, but all require an infectious insult as well as either an impairment in airway drainage or a defect in host defense.

Of the multiple etiologies of noncystic fibrosis bronchiectasis, only a few respond to direct treatment (eg, certain immunodeficiencies, nontuberculous mycobacterial infection, allergic bronchopulmonary aspergillosis). Instead, treatment of bronchiectasis is aimed at treating exacerbations, controlling chronic infection, reducing inflammation, and improving bronchial hygiene [1,2]. Surgical extirpation of affected areas may also be useful in selected patients.

The treatment of bronchiectasis will be reviewed here. The diagnosis and treatment of cystic fibrosis and the clinical manifestations, diagnosis and chronic management of bronchiectasis in adults are discussed separately.

(See "Cystic fibrosis: Clinical manifestations and diagnosis".)

(See "Cystic fibrosis: Overview of the treatment of lung disease".)

(See "Clinical manifestations and diagnosis of bronchiectasis in adults".)

(See "Bronchiectasis in adults: Maintaining lung health".)

ACUTE EXACERBATIONS — Patients with bronchiectasis have a high burden of bacterial pathogens and inflammation and exacerbations are generally associated with an increase or change in the bacterial population. Deciding when a patient has an acute exacerbation depends upon symptomatic changes.

Definition — In the absence of a specific diagnostic test, an exacerbation of bronchiectasis is defined as a deterioration in three or more of the following symptoms lasting at least 48 hours, accompanied by a change in bronchiectasis treatment and exclusion of other potential causes of clinical deterioration [3]:

Cough

Sputum volume and/or consistency

Sputum purulence

Breathlessness and/or exercise intolerance

Fatigue and/or malaise

Hemoptysis

Risk factors — The most reliable predictor of exacerbation is a history of prior exacerbations [4]. Patients with chronic bacterial infection, especially with Pseudomonas aeruginosa, are at great risk for exacerbations.

Respiratory viral infections are thought to trigger approximately 40 percent of exacerbations of bronchiectasis. In a one-year study of 119 patients with bronchiectasis, polymerase chain reaction (PCR) assays identified respiratory viral sequences (coronavirus, rhinovirus, and influenza) in nasopharyngeal and sputum samples more frequently during exacerbations as compared with steady state [5]. In addition, increases in inflammatory markers were more often associated with the virus positive than virus negative states.

The role of respiratory viruses in triggering exacerbations of bronchiectasis is further supported by a prospective analysis of 147 patients from an international registry of bronchiectasis in which exacerbations during the first year of the COVID-19 pandemic (March 2020 to March 2021) were 1.12/year compared with 2.08 and 2.01/year in each of the previous two years [6]. The percentage of patients with severe exacerbations requiring hospitalization was 9 percent in the pandemic year, compared with 14 and 16 percent in the two prior years. Only two patients suffered confirmed COVID-19 infections. Social distancing measures (eg, stay-at-home orders, mask wearing, social distancing) with reduction in viral exposures probably contributed to this dramatic decline in exacerbations.

Air pollution may increase the risk of exacerbations, particularly ones in which a particular pathogen is not identified [7]. One study suggested that relative immunoglobulin G2 (IgG2) subclass deficiency may also be associated with increased risk of exacerbations [8].

Clinical features — Acute bacterial infections are usually heralded by increased production of sputum that is more viscous and darker in color than baseline, and may be accompanied by lassitude, shortness of breath, pleuritic chest pain, or hemoptysis. Systemic complaints such as fever and chills are generally absent [3].

Lung examination may be normal or may reveal focal or diffuse crackles, sonorous wheezes (low pitched and continuous; also called rhonchi), or mid-inspiratory squeaks. Sibilant wheezes (higher pitched and whistling) may also be heard, particularly in patients with concomitant asthma.

Evaluation and diagnosis — Evaluation is focused on excluding other causes of worsening symptoms and identifying the specific pathogen(s) associated with the exacerbation. Complaints of fever, chills, or night sweats should prompt evaluation for pneumonia. Sputum is obtained for Gram stain and culture prior to antibiotic administration. A chest radiograph is performed in patients with respiratory distress or systemic complaints to exclude the possibility of pneumothorax or pneumonia.

The colonizing bacterial flora in patients with bronchiectasis is slightly different from that seen with chronic bronchitis. Frequently isolated pathogens in bronchiectasis include Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Pseudomonas aeruginosa (especially mucoid types), and, less frequently, Streptococcus pneumoniae [9,10]. The likelihood of resistant organisms tends to increase with the number of prior courses of antibiotics.

As exacerbations of bronchiectasis can be triggered by respiratory viral infection, we send nasal secretions for molecular tests for influenza and COVID-19 depending on local transmission patterns.

Sputum neutrophil elastase is an emerging biomarker candidate that may herald an exacerbation and correlate with antibiotic responsiveness, although it does not necessarily increase at the time of exacerbations [11,12].

Treatment — Antibiotic therapy is the cornerstone of treatment of exacerbations of bronchiectasis to reduce the bacterial load, which in turn reduces airway and systemic inflammatory mediators [1]. The initial antibiotic regimen for acute exacerbations of bronchiectasis is tailored to prior sputum cultures and sensitivities, when possible, rather than chosen empirically. Additional factors in antibiotic selection include determining whether to use oral or parenteral administration, the history of success or failure of prior regimens, and the presence of allergy or intolerance to antimicrobial agents. There is no role for inhaled antibiotics as sole agents in the setting of an acute exacerbation. For outpatients taking an oral antibiotic for an exacerbation, we suggest maintaining ongoing inhaled antibiotic therapy. If parenteral antibiotic(s) are administered, we suggest stopping the inhaled antibiotic and restarting shortly after completion of the IV course.

Oral antibiotic treatment — Most afebrile, clinically stable patients with an exacerbation of bronchiectasis can be treated with an oral antibiotic. The initial antibiotic selection should be guided by the most recent sputum culture results as well as patient experience with prior regimens.

Sputum culture data not available – For those without culture information, a fluoroquinolone (eg, levofloxacin, moxifloxacin) is a reasonable, broad spectrum, therapeutic option.

Sputum growing sensitive organisms – For patients whose sputum cultures do not show beta-lactamase-positive H. influenzae or Pseudomonas, reasonable initial antibiotic choices include amoxicillin 500 mg three times daily, or a macrolide, based on the typical colonization patterns noted above. Alternatively, other antibiotics with a similar spectrum of coverage may be used. The initial antibiotic selection can be modified based on the response to therapy and results of the sputum culture and sensitivity.

Sputum culture growing beta-lactamase-positive organism – In the presence of Moraxella catarrhalis or beta-lactamase producing H. influenzae, antibiotic choices include amoxicillin-clavulanate, a second or third generation cephalosporin, azithromycin or clarithromycin, doxycycline, or a fluoroquinolone [13]. (See "Moraxella catarrhalis infections", section on 'Treatment' and "Epidemiology, clinical manifestations, diagnosis, and treatment of Haemophilus influenzae", section on 'Directed treatment'.)

Sputum growing sensitive Pseudomonas – The virulence of Pseudomonas aeruginosa in sputum cannot be emphasized strongly enough. The presence of sputum Pseudomonas aeruginosa is associated with increased death, exacerbations, and hospital admissions [14-17]. For patients with known airway infection with Pseudomonas, the initial antibiotic selection depends on the sensitivity patterns of the organisms isolated. In the absence of known resistance to quinolones, the usual choice is ciprofloxacin, 500 to 750 mg twice daily [13]. However, if the patient has had prior courses of anti-pseudomonal agents, quinolone resistance often necessitates administration of intravenous antibiotics.

Because of the propensity of P. aeruginosa to develop resistance and the limited availability of oral agents, the efficacy of adding inhaled tobramycin solution (TS) to oral ciprofloxacin was studied. In a multicenter trial, 53 patients with known P. aeruginosa infection who were having exacerbations of bronchiectasis were randomly assigned to receive ciprofloxacin plus inhaled TS or ciprofloxacin plus placebo for two weeks [18]. The addition of inhaled TS to ciprofloxacin did not improve clinical outcomes compared to ciprofloxacin alone, although there was a marked reduction of Pseudomonas density in the sputum of patients who received inhaled TS plus ciprofloxacin. Wheezing was more common in the inhaled TS plus ciprofloxacin group.

Based on current data, inhaled aerosols of antibiotics, such as TS, cannot be recommended alone or in combination with ciprofloxacin for acute exacerbations in bronchiectasis. Certain aerosolized antibiotics may be helpful for prophylaxis. (See "Bronchiectasis in adults: Maintaining lung health", section on 'Inhaled antibiotics'.)

Duration of therapy – The optimal duration of therapy is not well-defined. Clinical experience favors a duration of 10 to 14 days for patients with a first time or few exacerbations [19,20]. The European Respiratory Society (ERS) guidelines released in 2017 suggest a 14-day course of antibiotics based on expert consensus, although they note that shorter and longer durations have not been directly compared [2]. Sputum culture and sensitivity to help define antibiotic selection are indicated in patients who fail to respond to the initial antibiotic, or who have repeated symptomatic attacks over a short period of time.

Intravenous treatment — The main reasons for intravenous antibiotic treatment are respiratory distress, hypoxemia, cardiopulmonary instability, and/or the presence of pathogens that are resistant to available oral agents. Initial inpatient treatment of an exacerbation is appropriate for patients with characteristics such as increased respiratory rate ≥25/minute, hypotension, temperature ≥38°C, hypoxemia (pulse oxygen saturation <92 percent), or failure to improve after oral antibiotics (and no facilities for home intravenous therapy) [13]. As with outpatient treatment, a sputum sample is obtained for bacteriologic culture prior to initiation of antibiotics. Blood cultures are obtained in patients with a fever ≥38°C or evidence of respiratory distress.

Sputum growing resistant Pseudomonas – The nonquinolone antibiotics typically used for resistant Pseudomonas require intravenous administration. Intravenous antibiotics for exacerbations due to resistant Pseudomonas are discussed below and separately. (See "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on 'Antibiotics with antipseudomonal activity'.)

If the patient has known airway infection with Pseudomonas that is resistant to oral quinolones, the initial antibiotic choice is based on the sensitivity profile from culture data and history of allergy to antibiotics.

It is controversial whether single or dual (eg, beta-lactam plus aminoglycoside) antibiotic therapy is preferable for flares of bronchiectasis due to Pseudomonas [13]. A meta-analysis of studies examining this question in patients with cystic fibrosis was unable to determine which course of therapy is better [21]. We typically use a single agent (eg, antipseudomonal penicillin, ceftazidime, or aztreonam) unless the patient appears acutely ill such that an incipient Pseudomonas pneumonia seems possible. In the latter case, we typically add a second agent (eg, fluoroquinolone, aminoglycoside). Aminoglycosides should not be used as monotherapy. The question of single versus dual therapy and antibiotic selection and dosing for Pseudomonas pneumonia are discussed in greater detail separately. (See "Pseudomonas aeruginosa pneumonia", section on 'Management' and "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on 'Role of combination antimicrobial therapy'.)

Use of aminoglycoside antibiotics requires careful dosing and monitoring to avoid renal or ototoxicity. (See "Dosing and administration of parenteral aminoglycosides".)

Sputum growing methicillin resistant Staphylococcus aureus (MRSA) – MRSA was isolated from the sputum of 18 percent of patients hospitalized for an exacerbation of bronchiectasis [22]. In hospitalized patients with MRSA in prior sputum samples or Gram-positive cocci in clusters on a current sputum Gram stain, the initial empiric regimen should include vancomycin (see "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults") or linezolid 600 mg every 12 hours (off-label).

Sputum culture data not available – For patients requiring hospital admission due to severe respiratory impairment who do not have sputum culture data, local antibiotic resistance patterns and responses to recent antibiotics guide empiric antibiotic selection. For example, if the patient has failed an oral quinolone, coverage for resistant Pseudomonas and MRSA should be included, pending updated culture results.

Duration and tailoring of therapy – Once the patient has stabilized and results of initial cultures are available, the antibiotic regimen can be narrowed to the most effective/least toxic regimen. For patients with resistant organisms such as P. aeruginosa or requiring intravenous antibiotics, a 14 day course is preferred [13].

Airway clearance – Inpatient therapy should include attention to airway clearance techniques (table 1), as described separately. (See "Bronchiectasis in adults: Maintaining lung health", section on 'Airway clearance therapy'.)

Antiviral therapy — Influenza antiviral therapy is usually indicated for patients whose exacerbation of bronchiectasis has been triggered by influenza virus, although the benefit of antiviral therapy wanes when presentation is >72 hours after symptom onset. The usual treatment is oral oseltamivir or baloxavir; intravenous peramivir can be used if the patient is unable to take oral medication. (See "Seasonal influenza in nonpregnant adults: Treatment".)

Specific therapy for COVID-19 should be individualized based on symptoms, risk factors for severe disease, time since symptom onset, and location of care, as described separately. (See "COVID-19: Management in hospitalized adults" and "COVID-19: Management of adults with acute illness in the outpatient setting".)

Atypical pathogens — Pathogens that are particularly problematic and difficult to eradicate are nontuberculous mycobacteria (NTM) and Aspergillus species.

Nontuberculous mycobacteria — M. avium, M. intracellulare, and M. abscessus are the most frequently isolated NTM and are responsible for the greatest clinical impact. A detailed discussion about the treatment of MAC and other nontuberculous mycobacteria in the lung is presented elsewhere. (See "Treatment of Mycobacterium avium complex pulmonary infection in adults" and "Microbiology of nontuberculous mycobacteria".)

Aspergillus species — Allergic bronchopulmonary aspergillosis (ABPA) is a cause of central bronchiectasis in patients with asthma and can also develop in patients with bronchiectasis due to another cause. Treatment of ABPA (eg, systemic glucocorticoids, antifungal agents, omalizumab) aims to control episodes of acute inflammation and limit progressive lung injury and is discussed separately. (See "Treatment of allergic bronchopulmonary aspergillosis", section on 'Treatment'.)

Outcomes after exacerbation — Symptoms of a bronchiectasis exacerbation last for a median of 16 days and approximately 16 percent of patients do not recover to baseline for more than one month, indicating that exacerbations lead to irreversible morbidity in some patients [23]. Patients with three or more exacerbations per year have twice the mortality rate of those who do not experience exacerbations (hazard ratio 2.03; 95% CI 1.02–4.03), after accounting for potential confounders [4]. Exacerbations requiring hospital admission more than double the subsequent mortality risk [4].

MANAGEMENT OF HEMOPTYSIS — Bleeding due to bronchiectasis is typically associated with acute infective episodes and is produced by injury to superficial mucosal neovascular bronchial arterioles. For most patients with hemoptysis complicating bronchiectasis, flexible bronchoscopy and chest computed tomography (CT) are complementary diagnostic tools to localize the bleeding to a lobe or segment. Once the site of bleeding is identified, bronchoscopic techniques such as balloon tamponade, topical application of a vasoconstrictive or coagulant agent, laser therapy, electrocautery, argon plasma coagulation, and cryotherapy may be able to stop the bleeding [24]. (See "Evaluation and management of life-threatening hemoptysis", section on 'Initial investigations'.)

If bronchoscopic techniques to control bleeding are unsuccessful or are not available, the next step is usually arteriographic embolization of bleeding sites (typically from a bronchial artery) by an interventional radiology service. Bronchial artery embolization successfully stops pulmonary hemorrhage in more than 85 percent of attempted embolizations. Bronchial artery embolization preserves lung tissue and often eliminates the need for surgery [25]. However, if embolization is unsuccessful and bleeding persists, surgical resection may be necessary [26]. Urgent surgery is occasionally required for the management of life-threatening hemoptysis due to bronchiectasis that cannot be controlled with less invasive measures. The evaluation and management of massive hemoptysis is discussed separately [24]. (See "Evaluation and management of life-threatening hemoptysis", section on 'Continued or recurrent life-threatening bleeding'.)

ADVANCED DISEASE

Resection of bronchiectatic lung — The immediate goal of surgical extirpation includes removal of the most involved segments or lobes with preservation of nonsuppurative or nonbleeding areas. Middle and lower lobe resections are most often performed. The superior segment of the lower lobe may be involved to a lesser extent and can frequently be salvaged when considering lower lobe resection. Surgical intervention is often combined with an aggressive antibiotic and bronchial hygiene regimen to reduce bacterial infection and improve drainage.

Major indications — The major indications and goals for resectional surgery in bronchiectasis include:

Removal of destroyed lung partially obstructed by a tumor or the residue of a foreign body

Reduction in acute infective episodes in patients with frequent exacerbations due to localized bronchiectasis

Reduction in overwhelming purulent and viscid sputum production in patients with bronchiectasis confined to one or two lobes and unresponsive to medical therapy

Elimination of bronchiectatic airways subject to uncontrolled hemorrhage when other measures fail (see 'Management of hemoptysis' above)

Removal of an area suspected of harboring resistant organisms such as nontuberculous mycobacteria (NTM) [27] or multidrug resistant tuberculosis (see "Treatment of Mycobacterium avium complex pulmonary infection in adults", section on 'Surgical management' and "Treatment of drug-resistant pulmonary tuberculosis in adults")

Outcomes — Surgical case series have shown low operative mortality (<2 percent) and resolution or improvement of symptoms in the majority of patients selected to receive surgery [26,28-32]. The following studies illustrate typical outcomes that follow surgical resection:

In the largest study from the past two decades, 790 Chinese patients (mean age 47 years) were followed for a mean of four years following lung resection (segmentectomy, lobectomy, pneumonectomy) [29]. Mortality at 30 days was 1.1 percent. Seventy-five percent of patients became asymptomatic or were improved, while 15 percent were unimproved or worse.

In a study from the United States, 134 patients (mean age 48 years) were followed for a mean of six years [26]. Mortality was 2 percent and 89 percent of patients improved.

Postoperative complications include empyema, hemorrhage, prolonged air leak, and poorly expanding remaining lung due to persistent atelectasis or suppuration. In selected patients, video-assisted thoracoscopic surgery (VATS) segmentectomy or lobectomy may be possible and allow fewer complications and shorter hospitalizations. Pleural adhesions may require conversion to thoracotomy [30].

Lung transplantation — With bilateral lung transplantation, the survival advantage of transplantation is comparable to that seen in other diagnostic groups, including cystic fibrosis [33,34]. According to the Organ Procurement and Transplant Network (OPTN) database maintained by the United Network for Organ Sharing (UNOS), 407 patients with bronchiectasis underwent lung transplantation in the United States between 1992 and 2019 [35]. The mean age was 47 years and the median transplant list waiting time was 254 days. The median survival time post-transplant was 5.5 to 6.0 years. (See "Lung transplantation: An overview" and "Lung transplantation: General guidelines for recipient selection".)

FUTURE DIRECTIONS — Experts from the United States [36] and Europe [37] have suggested that research priorities in bronchiectasis should include epidemiology, pathogenesis, and management [37]. (See "Exhaled nitric oxide analysis and applications", section on 'Bronchiectasis and cystic fibrosis'.)

Culture-independent microbial gene surveys – Culture-independent microbial gene surveys of airway secretions from individuals with noncystic fibrosis bronchiectasis have identified a broader array of microbial species, including anaerobic bacteria that are not identified by routine culture [38]. And, a 16-year longitudinal study showed that sputum microbial communities remain relatively stable [39].

In studies of the airway microbiome, greater bacterial diversity is associated with better clinical parameters, including a higher forced expiratory volume in one second (FEV1) and fewer symptoms, suggesting that low diversity may reflect overgrowth by pathogenic bacteria such as P. aeruginosa [40]. Moreover, the clustering of organisms, particularly in association with Pseudomonas, correlates with exacerbations of bronchiectasis. Antibiotic treatment reduces this clustering or the so-called interactome [41]. Use of this technology does not yet have clinical applicability.

Investigative method of palliation for P. aeruginosa infection – Some patients with bronchiectasis have excess IgG2 specific to the bacterial O-antigen, which (unlike other antibodies) inhibits immune killing of P. aeruginosa in serum samples. Two patients with bronchiectasis, severe respiratory insufficiency, P. aeruginosa airway infection, and frequent exacerbations had elevated IgG2 serum levels and impaired serum killing of P. aeruginosa [42]. Plasmapheresis sessions followed by intravenous pooled immune globulin infusions for five days markedly improved their clinical status including reduction of days in the hospital and average days on intravenous antibiotics assessed up to 8 to 12 months. Cultures for P. aeruginosa remained negative for three months, IgG2 levels were lowered, and ability to kill P. aeruginosa was improved.

Enhancing treatment adherence – Bronchiectasis is a complex chronic disease that often involves following a difficult and cumbersome management plan with multiple oral and nebulized medications and bronchial hygiene maneuvers throughout the day. Many of the treatments for bronchiectasis involve the use of off-label and expensive medications, prolonged administration time, and sometimes distressing adverse effects. Adherence to treatments involves patient-specific and treatment-related constraints. A pilot study involving a structured interview process has begun to explore factors to enhance treatment adherence among patients with bronchiectasis [43].

Elastase inhibitor – Dipeptidyl peptidases activate neutrophil serine proteases (NSPs; eg, neutrophil elastase), and excess activation of NSPs is thought to contribute to perpetuation of inflammation and lung destruction in bronchiectasis, raising the possibility that a reversible inhibitor of dipeptidyl peptidase 1 (eg, brensocatib; INS1007) might reduce the rate of exacerbations. In the phase 2 randomized WILLOW trial with 256 participants who had at least two exacerbations in the prior year, brensocatib was administered in one of two doses, 10 mg or 25 mg, and compared with placebo [44]. During the 24-week treatment, 42 exacerbations occurred in the 25 mg brensocatib group, 34 in the 10 mg brensocatib group and 54 in the placebo group. The time to first exacerbation was prolonged with brensocatib compared with placebo (brensocatib 10 mg versus placebo, p=0.03; brensocatib 25 mg versus placebo, p=0.04). Overall, brensocatib was well-tolerated; headache and dyspnea were the only common adverse events that occurred more often in the 25 mg group than placebo, but the numbers were small.

Treatment based on eosinophilic endotype - In a re-examination of a study that included subjects with obstructive lung diseases (asthma, chronic obstructive pulmonary disease [COPD], bronchiectasis) with increased blood eosinophils who were treated with inhaled fluticasone, the bronchiectasis subjects had improved quality of life (QOL) [45]. In a bronchiectasis referral center in Germany, 49 participants (11 percent) had eosinophils >300 cells/microL and of these, 21 had frequent exacerbations and were considered refractory to an aggressive management strategy [46]. Based on this eosinophilic endotype, twelve received an interleukin (IL)-5 antagonist (mepolizumab) and nine received an IL-5 alpha antagonist (benralizumab). At 6 months, significant improvements were noted in FEV1 and QOL, and a trend towards reduced exacerbation frequency.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bronchiectasis" and "Society guideline links: Primary ciliary dyskinesia" and "Society guideline links: Hemoptysis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Basics topic (see "Patient education: Bronchiectasis in adults (The Basics)")

SUMMARY AND RECOMMENDATIONS

Definition – Bronchiectasis is a condition of chronic cough and viscid sputum production confirmed by chest computed tomography (CT) showing airway dilation and bronchial wall thickening. Exacerbations are usually characterized by acute bacterial infection, although the trigger may be a viral infection. (See 'Introduction' above and 'Acute exacerbations' above.)

Deciding when a patient has an acute exacerbation depends upon symptomatic changes rather than any specific laboratory feature. In the absence of a specific diagnostic test, an exacerbation of bronchiectasis is defined as a deterioration in three or more of the following symptoms: cough, change in sputum volume and/or consistency, sputum purulence, breathlessness and/or exercise intolerance, fatigue and/or malaise, and hemoptysis. The symptoms should have lasted at least 48 hours, and other potential causes of clinical deterioration should have been excluded. By definition, exacerbations of bronchiectasis are accompanied by a change in bronchiectasis treatment. (See 'Definition' above.)

Evaluation – Evaluation is focused on excluding other causes of worsening symptoms and identifying the specific pathogen(s) associated with the exacerbation. Complaints of fever, chills, or night sweats should prompt evaluation for pneumonia. Sputum is obtained for Gram stain and culture prior to antibiotic administration. Molecular tests for influenza and COVID-19 are obtained on samples of nasal secretions depending on local transmission patterns. A chest radiograph is performed in patients with respiratory distress or systemic complaints to exclude the possibility of pneumothorax or pneumonia. (See 'Evaluation and diagnosis' above.)

Initial antibiotic regimen – The initial antibiotic regimen for acute exacerbations of bronchiectasis is tailored to prior sputum cultures and sensitivities, rather than chosen empirically. Additional factors in antibiotic selection include oral versus parenteral administration, the history of success or failure of prior regimens, and the presence of allergy to antimicrobial agents. (See 'Treatment' above.)

Outpatients: recent cultures without resistant organisms – For outpatients with sputum cultures that do not show beta-lactamase-positive H. influenzae or Pseudomonas, reasonable initial antibiotic choices include amoxicillin 500 mg three times daily, or a macrolide. In the presence of beta-lactamase producing organisms, choices include amoxicillin-clavulanate, second or third generation cephalosporin, doxycycline, or a fluoroquinolone. (See 'Oral antibiotic treatment' above.)

Outpatients: multiple prior exacerbations/no recent sputum data – For outpatients with multiple prior exacerbations or no recent sputum culture data, we suggest initiation of a fluoroquinolone antibiotic (eg, levofloxacin, moxifloxacin), rather than an alternative oral antibiotic. (Grade 2C). (See 'Acute exacerbations' above.)

Hospitalized patients – For hospitalized patients with an acute exacerbation, we suggest initiation of an intravenous antibiotic with efficacy for P. aeruginosa (Grade 2B). Alternatively, for patients who are acutely ill and have a history of growing resistant strains of P. aeruginosa, we select two anti-pseudomonal antibiotics that have different mechanisms of action, although the need for dual therapy is controversial. If sputum cultures have grown methicillin resistant Staphylococcus aureus (MRSA), empiric coverage with vancomycin or linezolid should be included. (See 'Intravenous treatment' above.)

Duration – For treatment of acute exacerbations, we suggest 10 to 14 days of antibiotic therapy rather than a shorter course (Grade 2C). Occasionally, a longer course is needed if the patient has resistant organisms or is improved but not yet back to baseline. (See 'Acute exacerbations' above.)

Antiviral therapy – Influenza antiviral therapy is usually indicated for patients whose exacerbation of bronchiectasis has been triggered by influenza virus, although the benefit of antiviral therapy wanes when presentation is >72 hours after symptom onset. The usual treatment is oral oseltamivir or baloxavir; intravenous peramivir can be used if the patient is unable to take oral medication. (See 'Antiviral therapy' above.)

For patients whose exacerbation was triggered by COVID-19, specific therapy for COVID-19 should be individualized based on symptoms, risk factors for severe disease, time since symptom onset, and location of care, as described separately. (See "COVID-19: Management in hospitalized adults" and "COVID-19: Management of adults with acute illness in the outpatient setting".)

Hemoptysis – Patients with life-threatening hemoptysis due to bronchiectasis may require one or more interventions to stop the bleeding; chest computed tomography (CT) and bronchoscopy are considered complementary to help localize the site of bleeding. For patients with brisk hemoptysis, bronchial artery embolization or resectional surgery may be required to halt or palliate the bleeding. (See 'Management of hemoptysis' above and 'Resection of bronchiectatic lung' above and "Evaluation and management of life-threatening hemoptysis".)

Advanced disease – Surgical resection and lung transplantation are used to manage selected patients refractory to medical therapy (eg, recurrent or severe hemoptysis, frequent exacerbations despite therapy, advanced lung disease). (See 'Advanced disease' above and 'Lung transplantation' above.)

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Topic 1435 Version 63.0

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