Cystic Fibrosis - Management of Pulmonary Exacerbations - UpToDate

20/1/24, 22:55 Cystic fibrosis: Management of pulmonary exacerbations - UpToDate
Official reprint from UpToDate®

www.uptodate.com © 2024 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Cystic fibrosis: Management of pulmonary

exacerbations
AUTHOR: Richard H Simon, MD
SECTION EDITOR: James F Chmiel, MD, MPH
DEPUTY EDITOR: Alison G Hoppin, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2023.

This topic last updated: Oct 30, 2023.
INTRODUCTION
Cystic fibrosis (CF) is a multisystem disorder caused by pathogenic variants in the CFTR gene
(CF transmembrane conductance regulator) [1,2]. (See "Cystic fibrosis: Genetics and
pathogenesis".)
Pulmonary disease remains the leading cause of morbidity and mortality in people with CF
[3], and pulmonary exacerbations are associated with accelerated loss of lung function,
decreased quality of life, and increased mortality [4-7]. The causes of pulmonary
exacerbations are multifactorial, with infection playing an important but somewhat ill-
defined role [8]. The development of treatments that reduce the frequency and severity of
pulmonary exacerbations is an important contributor to the marked improvements in
survival of people with CF ( figure 1).
Considerable variation exists in how patients with CF are treated for pulmonary
exacerbations [9-12], despite the availability of clinical guidelines [13-16]. The
recommendations in this topic review generally adhere to published guidelines and/or
conform to common clinical practices.
Treatment of pulmonary exacerbations in CF is multifaceted, involving antibiotics, chest

physiotherapy, inhaled medications to promote secretion clearance, and, sometimes,
antiinflammatory agents. An overview of these interventions will be reviewed here. Selection
of antibiotics for pulmonary exacerbations is discussed in a separate topic review. (See
"Cystic fibrosis: Antibiotic therapy for pulmonary exacerbations".)
https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&so… 1/31

Other aspects of pulmonary disease in CF are discussed in separate topic reviews:
● (See "Cystic fibrosis: Overview of the treatment of lung disease".)
● (See "Cystic fibrosis: Treatment with CFTR modulators".)
● (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection".)
● (See "Cystic fibrosis: Clinical manifestations of pulmonary disease".)
● (See "Cystic fibrosis: Management of advanced lung disease".)
PULMONARY EXACERBATIONS IN CYSTIC FIBROSIS
Definition — The clinical course of most patients with CF is punctuated by acute episodes of
worsening pulmonary status that are referred to as "pulmonary exacerbations" [17,18]. The
CF field has not reached a consensus definition of pulmonary exacerbation for the purposes
of patient care or clinical research [19,20]. In many clinical trials, exacerbations were defined
solely on the criterion that a participant's CF clinician initiated antibiotic treatment for an
acute worsening of clinical status [10,21]. Other trials have defined exacerbations based on
specific symptoms and signs, but these criteria do not perform well at identifying those
patients whose CF clinicians choose to treat with antibiotics [19,20]. Part of the difficulty may
be that pulmonary exacerbations are not a single entity but have differing etiologies,
inflammatory profiles, and clinical outcomes [22,23].
Diagnosis — In clinical practice, a pulmonary exacerbation is diagnosed based on changes

from an individual patient's recent baseline health status [24], typically including several of
the following symptoms and signs:
● Symptoms:
• New or increased cough

• New or increased sputum production or chest congestion
• Decreased exercise tolerance or new or increased dyspnea with exertion or at rest
• Increased fatigue
• Decreased appetite and possible weight loss
• Increased respiratory rate at rest
• Change in sputum appearance
• Hemoptysis
• Fever (present in a minority of patients)
• Increased nasal congestion or drainage

● Pulmonary function tests – Reductions in pulmonary function as measured by forced

expiratory volume in one second (FEV1) are often present during pulmonary
exacerbations but are not required for its diagnosis, although large decrements in FEV1
(eg, more than a 10 percent decline from baseline) are more likely to cause clinicians to
initiate treatment in patients presenting with typical signs and symptoms of an
exacerbation [25]. Although it was hypothesized that routine monitoring by home
spirometry would promote earlier detection of pulmonary exacerbations and therefore
better outcomes, a randomized 52-week study in which people with CF were monitored
twice weekly with home spirometry failed to detect long-term benefit relative to usual
management, as measured by rate of decline of FEV1 [26]. Contrasting results were
found in a report from another CF center that instituted a new protocol in which a drop
in FEV1 (≥5 points from baseline) triggered treatment for a pulmonary exacerbation and
reported subsequent improvement in mean FEV1 across the center's patient population
[27].
● Other – Chest radiographs may not show significant changes over baseline and are not
routinely obtained for people with mild symptoms. A decrease in arterial hemoglobin
oxygen saturation may occur but is not required to diagnose an exacerbation.
There are no absolute thresholds that determine a pulmonary exacerbation. For example, an
individual who is asymptomatic at baseline is typically considered to have a pulmonary
exacerbation if there is a new cough with sputum production, fatigue, and decreased
appetite, even though FEV1 may remain in normal range [28].
Severity grading — CF clinicians routinely distinguish mild from severe exacerbations when
planning treatment [9,29], although there are no protocols for severity grading [30]. A
common approach is to consider the degree of worsening from baseline of each of the
patient's signs and symptoms and arrive at a global assessment of the extent of decline. As
examples:
● In an individual with mild pulmonary disease at baseline, an exacerbation is considered

severe if the acute illness is characterized by the onset of a productive cough and a
large decline in FEV1 (eg, greater than 10 percent).
● In an individual with severe pulmonary disease at baseline, an exacerbation is

considered mild if the cough, sputum production, exercise tolerance, and FEV1
worsened minimally but perceptibly from prior baseline status.
Incidence — In 2022, the Cystic Fibrosis Foundation Patient Registry reported that 10
percent of children and 15 percent of adults had at least one pulmonary exacerbation severe
enough to be treated with intravenous antibiotics, down from 23 percent of children and 43
percent of adults in 2018 [3]. A major driver of the decreased incidence is the availability of

the highly effective CF transmembrane conductance regulator (CFTR) modulator elexacaftor-

tezacaftor-ivacaftor, which brings treatment to approximately 94 percent of patients ≥6 years
of age (see "Cystic fibrosis: Treatment with CFTR modulators"). The improvement was
probably also related to changes in exposure to respiratory viruses during the coronavirus
disease 2019 (COVID-19) pandemic due to social distancing and mask wearing [31].
The risk of pulmonary exacerbation increases with age, female sex, declining lung function,
CF-related diabetes, and cirrhosis [32]. A strong predictor of developing a pulmonary
exacerbation is having had one or more exacerbations during the previous year. Other risk
factors include nonadherence to chronic CF treatments and depression [33,34].
PATHOGENESIS
Viruses — Viruses are detected in many cases of acute exacerbations in children with CF, and
there is some evidence that they are important contributors to declining pulmonary function.
Among children with a pulmonary exacerbation during the winter months, viruses were
detected by a molecular method in 34 to 60 percent [35,36]. The pathogens were
coxsackie/echovirus, rhinovirus/enterovirus, respiratory syncytial virus, parainfluenza,
adenovirus, and influenza. Among adults with pulmonary exacerbations, viruses were
detected in 10 to 25 percent, especially rhinovirus, enterovirus, respiratory syncytial virus,
parainfluenza virus, coronaviruses, and influenza [37-39].
Bacteria — Most people with CF have chronic bacterial infection of the airways, as
demonstrated by sputum cultures; the prevalence of each bacterial type varies with the age
of the patient ( figure 2). (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary
infection", section on 'Pathogens'.)
Important pathogens include ( table 1):
● Pseudomonas aeruginosa
● Staphylococcus aureus (methicillin-sensitive or methicillin-resistant species)
● Burkholderia cepacia complex
● Nontypeable Haemophilus influenzae
● Stenotrophomonas maltophilia
● Achromobacter species
● Nontuberculous mycobacteria
Anaerobic bacteria are frequently identified, but their role in pulmonary exacerbations is
uncertain [40-42]. Nonculture-based assays to identify bacteria have shown that the number
of species present in respiratory secretions from CF patients is often considerably higher

than what is revealed by culture-based methods, with substantial variation among patients
[43].
Although bacteria are clearly involved in the pathophysiology of pulmonary exacerbations in

CF, the mechanisms are uncertain [8,44]. Most exacerbations are not associated with the
appearance of new bacterial species or strains. Furthermore, there is no consistent pattern
of change in bacterial communities leading up to pulmonary exacerbations [43].
Inflammation — The CF airway is characterized by chronic neutrophil-rich inflammation (see

"Cystic fibrosis: Clinical manifestations of pulmonary disease"). Inflammatory markers in
serum and airway secretions increase during pulmonary exacerbations [22,45,46] and
decrease with treatment [47]. Although pulmonary infection is a major contributor to the
airway inflammation, there is some evidence that CF transmembrane conductance regulator
(CFTR) deficiency itself can cause inflammation in the absence of infection [48]. During an
exacerbation, bacterial or viral infection induces further inflammation, which contributes to
the lung damage. As a result, some antiinflammatory strategies are effective at limiting lung
damage. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on
'Antiinflammatory therapy'.)
SITE OF CARE
Severe pulmonary exacerbations usually require hospitalization to adequately manage the

complex regimen; closely monitor symptoms and laboratory test results; and ensure
intensive airway clearance therapy, nutrition, and rest.
Home management of exacerbations
● Mild exacerbations – Most mild exacerbations can be managed in an outpatient

setting, using oral and/or inhaled antibiotics and intensified airway clearance therapies.
Clinical care should include counseling to encourage close adherence to the regimen
and close follow-up to monitor progress. Some patients with mild exacerbations will still
require hospitalization and/or intravenous antibiotics, particularly if they show
inadequate improvement or if they have failed outpatient oral/inhaled regimens during
prior episodes. (See "Cystic fibrosis: Antibiotic therapy for pulmonary exacerbations",
section on 'Severity of the exacerbation'.)
● Moderate exacerbations – Moderate or severe pulmonary exacerbations are often

managed in an inpatient setting. However, home management may be appropriate for
select patients with nonsevere exacerbations and sufficient support to ensure optimal
treatment. When considering home therapy for a pulmonary exacerbation, resources
must be available at home to replicate the hospital program, including the prescribed

antibiotics and close adherence to airway clearance therapies (inhaled agents and chest
physiotherapy), with provisions for rest and good nutrition [13]. Children require
greater assistance than adults to accomplish these goals, and adult supervision is
needed even for teenagers. In considering home treatment for children, one must
consider the impact of lost work hours, the number of other children in the household,
the number and competence of available adult caregivers, and family stress before
deciding whether home treatment is preferable to hospitalization.
Concern over hospital costs as well as the preference of many patients have
encouraged home treatment with intravenous antibiotics for pulmonary exacerbations
in CF. Although studies vary in their conclusions, a preponderance of evidence suggests
that in-hospital treatment may be more effective. This was shown in a large prospective
study of standardized care for pulmonary exacerbations (STOP2 study [21]), in which 33
percent of participants received treatment exclusively in hospital, 21 percent exclusively
at home, and 46 percent initiated in hospital and completed at home [49]. The mean
increase in percent predicted forced expiratory volume in one second (FEV1) of those
treated only in hospital (8.0, 95% CI 6.7-9.4) was significantly better than those treated
only at home (5.0, 95% CI 3.5-6.5) or at both locations (7.0, 95% CI 5.9-8.1). Because the
participants were not randomly assigned to treatment location, sophisticated statistical
analyses were used to adjust for assignment bias in these studies, but residual bias
cannot be excluded. Similar conclusions were reached in another registry-based study
of 4497 pulmonary exacerbations, which found that recovery of FEV1 to ≥90 percent of
baseline level was 9.1 percent more likely when all treatment was delivered in-hospital
compared with treatment delivered entirely at home [50]. By contrast, some earlier and
smaller studies detected no significant differences in outcomes for patients treated
with intravenous antibiotics at home, including one very small randomized trial (31
exacerbations, 17 participants) [51,52] and an observational study (1535 participants)
[53].
Intensive care unit treatment — Indications for intensive care unit (ICU) care include:
● Respiratory insufficiency requiring respiratory support (see 'Respiratory support' below)

● Pneumothorax (see "Cystic fibrosis: Overview of the treatment of lung disease", section
on 'Spontaneous pneumothorax')
● Severe hemoptysis (see "Cystic fibrosis: Overview of the treatment of lung disease",
section on 'Hemoptysis')
Outcomes for adults and children with CF who require ICU care were previously reported to
be uniformly poor [54] but have fortunately improved [55,56]. Advanced CF lung disease
should not be considered a contraindication to mechanical ventilation or ICU care in general,

regardless of the patient's lung transplant status [57]. (See "Cystic fibrosis: Management of
advanced lung disease", section on 'Intensive care unit treatment'.)
An episode of respiratory failure should prompt discussion of end-of-life care, quality of life,
and possible indications for lung transplantation. Ideally, these discussions should occur
when a patient's clinical trajectory suggests increasing risk for respiratory failure but well
before ICU care is needed. (See "Cystic fibrosis: Management of advanced lung disease",
section on 'Lung transplant evaluation'.)
TREATMENT
The goals of treatment are to return the patient's symptoms to baseline and recover any lost
forced expiratory volume in one second (FEV1), which are not always possible. (See
'Prognosis' below.)
Antibiotics — Treatment of exacerbations with systemic antibiotics is a mainstay of CF care

and is recommended in virtually all consensus guidelines. Selection and dosing of antibiotics
are summarized in the table ( table 2) and discussed separately. (See "Cystic fibrosis:
Antibiotic therapy for pulmonary exacerbations".)
Periodic elective hospitalization for preventive therapy (referred to as "clean outs") is not
recommended, as reviewed separately. (See "Cystic fibrosis: Antibiotic therapy for chronic
pulmonary infection", section on 'Periodic hospitalizations'.)
Continuation of the chronic treatment regimen — The patient's chronic treatment

regimen should be continued or intensified during an acute exacerbation, as recommended
by virtually all guidelines, although high-quality studies are generally lacking to assess this
strategy [13]. The role for inhaled antibiotics during pulmonary exacerbations is uncertain.
(See "Cystic fibrosis: Antibiotic therapy for pulmonary exacerbations", section on 'Managing
the chronically prescribed antibiotics'.)
Key components include:
● CF transmembrane conductance regulator (CFTR) modulators. (See "Cystic fibrosis:

Treatment with CFTR modulators".)
● Airway clearance therapy, with inhaled agents (eg, inhaled dornase alfa or hypertonic
saline) and chest physiotherapy. (See "Cystic fibrosis: Overview of the treatment of lung
disease", section on 'Airway clearance therapies'.)
● Antiinflammatory medications (eg, azithromycin, ibuprofen) in selected patients.

Decisions about continuing or suspending azithromycin during a pulmonary
exacerbation are discussed separately. (See "Cystic fibrosis: Antibiotic therapy for
pulmonary exacerbations", section on 'Managing the chronically prescribed antibiotics'

and "Cystic fibrosis: Overview of the treatment of lung disease", section on
'Antiinflammatory therapy'.)
● Optimization of nutritional status. (See "Cystic fibrosis: Nutritional issues", section on

'Nutrition support'.)
● Ensuring glucose control for those with CF-related diabetes. (See "Cystic fibrosis-related
diabetes mellitus", section on 'Treatment'.)
● Exercise, as tolerated. (See "Cystic fibrosis: Overview of the treatment of lung disease",
section on 'Chest physiotherapy'.)
Many patients have poor adherence to these treatments when they are at their baseline
status and require encouragement to increase their use during exacerbations [33]. If
possible, the frequency of airway clearance treatments should be increased during
exacerbations beyond what is prescribed as part of the chronic therapy regimen (eg,
increasing to four times per day), as recommended by Cystic Fibrosis Foundation guidelines
[13].
Other medications (for selected patients)
Bronchodilators — During pulmonary exacerbations, our practice is to administer short-

acting bronchodilator medications:
● Prior to airway clearance therapy and exercise

● Prior to other inhaled medications for those who develop bronchial constriction in
response to them
● As a rescue medication for those with airway hyperreactivity
We use these same indications for bronchodilators during baseline health. (See "Cystic
fibrosis: Overview of the treatment of lung disease", section on 'Bronchodilators'.)
Evidence supporting routine use of bronchodilators during pulmonary exacerbations is

limited. Poor responsiveness to bronchodilators was reported in a retrospective study in
which the median bronchodilator-induced increase in FEV1 was only 4.3 percent and only 9
percent of the participants met standard criteria for being responsive to bronchodilator
treatment [58]. Somewhat better bronchodilator responsiveness was shown in a randomized
crossover study that compared the effects of albuterol with placebo (normal saline) in 24
hospitalized patients who were evaluated after they had been on antibiotic therapy for at
least six days [59]. A significant increase in FEV1 was seen 45 minutes following albuterol
administration but not following normal saline (mean FEV1 increase 14.8 versus 1 percent).
However, by the following morning, there was no between-group difference in FEV1. No

studies have evaluated more prolonged effects of bronchodilators on pulmonary

exacerbations, eg, duration of antibiotic treatment, recovery to baseline FEV1, or
improvement in symptoms.
Glucocorticoids — There is considerable variation in practice regarding use of

glucocorticoids for pulmonary exacerbations, and evidence is limited [11,60].
Our practice is to administer a course of prednisone (2 mg/kg/day [maximum 60 mg daily]

for five days) to the small subset of CF patients whose exacerbations have characteristics of
an acute asthmatic episode (eg, chest tightness, wheezing, acute symptomatic response to
inhaled beta-adrenergic agonists). We use this strategy because glucocorticoids are
beneficial for asthmatic symptoms in patients without CF. (See "Acute asthma exacerbations
in children younger than 12 years: Emergency department management", section on
'Systemic glucocorticoids' and "Acute exacerbations of asthma in adults: Home and office
management", section on 'Initiation of oral glucocorticoids'.)
Other CF clinicians administer a brief course of glucocorticoids for all patients with
exacerbations, regardless of the presence of asthma-like symptoms. This strategy is based
on the assumption that acute exacerbations in CF are similar to acute exacerbations of
chronic obstructive pulmonary disease (COPD) in adults (see "COPD exacerbations:
Management"). However, we do not use this approach, because the few available studies
suggest that systemic glucocorticoids do not improve pulmonary outcomes in people with CF
and may contribute to dysglycemia [61-63].
Another strategy used by some clinicians is to administer systemic glucocorticoids to

patients whose response to initial treatment is deemed suboptimal. Because of the scarcity
of data evaluating glucocorticoids for pulmonary exacerbations, the Cystic Fibrosis
Foundation did not make a recommendation regarding their use [13]. A clinical trial is
underway that is evaluating the efficacy and safety of oral prednisone as adjunctive
treatment for people with insufficient response to initial antibiotic treatment
( NCT03070522).
Antiviral agents
● Influenza – Antiviral treatment is indicated for people with CF with known or suspected
influenza because they are at high risk for severe or complicated disease. Antiviral
treatment should be initiated regardless of the duration of symptoms or severity of
initial illness, although it is likely to have the greatest benefit if it is initiated within 48
hours after symptom onset. Indications and regimens are discussed separately. (See
"Seasonal influenza in children: Management", section on 'Antiviral therapy' and
"Seasonal influenza in nonpregnant adults: Treatment".)

Annual vaccination against viral influenza is recommended for all CF patients older than
six months of age, using an inactivated vaccine delivered by injection. Vaccination is
highly preferred over the use of pre- or postexposure chemoprophylaxis [64]. (See
"Cystic fibrosis: Overview of the treatment of lung disease", section on 'Prevention of
infection'.)
● COVID-19 – CF is a condition associated with a higher risk of developing severe COVID-

19 disease, according to the United States Centers for Disease Control and Prevention
(CDC). Patients with CF should follow CDC recommendations for higher-risk individuals
regarding vaccination and treatment of infection (see "COVID-19: Vaccines" and
"COVID-19: Management in children" and "COVID-19: Management of adults with acute
illness in the outpatient setting"). Of note, nirmatrelvir-ritonavir, which is used to treat
mild to moderate COVID-19 disease in adults, is a strong cytochrome P450 3A4 (CYP3A)
inhibitor and will reduce the clearance of CFTR modulators. Administration of
nirmatrelvir-ritonavir requires large reductions in modulator doses [65]; consultation
with a pharmacist is advisable.
Respiratory support
● Supplemental oxygen – We administer supplemental oxygen as needed during

pulmonary exacerbations, targeting an oxygen hemoglobin saturation by pulse
oximetry of 88 to 92 percent or an arterial blood oxygen tension of 60 to 70 mmHg.
This approach is based on the guidelines that are used for patients with acute
exacerbations of COPD. No CF-specific clinical trials of supplemental oxygen
administration have been performed that would modify these COPD recommendations.
After initiation of supplemental oxygen, patients should be monitored for deterioration
in mental status due to hypercapnia, although the incidence of this complication is low.
(See "COPD exacerbations: Management".)
● Noninvasive ventilation – We offer noninvasive positive pressure ventilation to

patients who develop acute respiratory failure (eg, acute elevation of arterial carbon
dioxide tension to >45 mmHg or hypercapnic acidosis) and who have none of the
contraindications (eg, severely impaired consciousness, inability to cooperate, or
inability to protect their airway). The noninvasive ventilation regimen must
accommodate intermittent treatments for assisting airway secretion clearance (inhaled
airway clearance medications and chest physiotherapy). The decisions are consistent
with guidelines for people with COPD who develop acute ventilatory failure during
exacerbations. (See "Noninvasive ventilation in adults with acute respiratory failure:
Benefits and contraindications".)
The possibility that noninvasive ventilation might enhance airway clearance therapy
was evaluated in a randomized study of 38 participants admitted for treatment of a
https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&s… 10/31
pulmonary exacerbation [66]. There was no significant increased rate of improvement

in FEV1 or symptom scores in the noninvasive ventilation group [66]. Thus, we do not
recommend noninvasive ventilation for the purposes of enhancing airway clearance
therapy.
● Invasive ventilation – CF patients with acute respiratory failure are candidates for
endotracheal intubation and mechanical ventilation, if noninvasive ventilation fails and
if the intervention is congruent with the patient's goals of care. The decisions are
consistent with guidelines used for people with COPD and acute respiratory failure.
(See "Invasive mechanical ventilation in acute respiratory failure complicating chronic
obstructive pulmonary disease".)
Input from the appropriate transplant center should be sought to determine how
intubation with mechanical ventilation will affect the patient's listing for
transplantation. (See "Cystic fibrosis: Management of advanced lung disease".)
● Extracorporeal membrane oxygenation support (ECMO) – When adequate

ventilation and/or oxygenation cannot be supported by assisted ventilation, ECMO has
been used to successfully bridge CF patients to lung transplantation [67,68]. (See
"Cystic fibrosis: Management of advanced lung disease", section on 'Intensive care unit
treatment'.)
Individuals who require invasive ventilation should also be considered for early
institution of ECMO, if this is congruent with the patient's goals of care and with input
from the pertinent transplant center, as outlined in Cystic Fibrosis Foundation
guidelines for advanced CF lung disease [57]. (See "Extracorporeal life support in adults
in the intensive care unit: Overview".)
PROGNOSIS
Following a pulmonary exacerbation, recovery of the forced expiratory volume in one second
(FEV1) decrement is often incomplete. With each exacerbation, between 12 and 35 percent of
patients fail to recover to at least 90 percent of their baseline FEV1 [10,69,70]. Quality of life
also declines with increasing numbers of pulmonary exacerbations [6]. Following treatment
of a pulmonary exacerbation, symptomatic improvements are not well correlated with FEV1
recovery [71]. As an example, in a prospective study of 58 adults with CF, 23 percent of
pulmonary exacerbations were associated with ongoing symptoms after 14 days of
antibiotics, with further symptomatic improvement when treatment was extended to 21 days
[72]. However, continuation of antibiotic treatment was not associated with further
improvement in FEV1 or body mass index. These observations are relevant to decisions about

duration of treatment. (See "Cystic fibrosis: Antibiotic therapy for pulmonary exacerbations",
section on 'Duration of treatment'.)
Given the adverse consequences of exacerbations, reducing exacerbation frequency is an

important rationale for many of the chronic treatments for CF pulmonary disease. (See
"Cystic fibrosis: Overview of the treatment of lung disease" and "Cystic fibrosis: Antibiotic
therapy for chronic pulmonary infection" and "Cystic fibrosis: Treatment with CFTR
modulators".)
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: Cystic fibrosis".)
SUMMARY AND RECOMMENDATIONS
● Definition – In clinical practice, a pulmonary exacerbation is diagnosed based on a

clinician's global assessment of changes from the patient's recent baseline health
status, including changes in symptoms (cough, sputum production, exercise tolerance)
with or without changes in pulmonary function tests. (See 'Diagnosis' above.)
● Pathogenesis – The clinical course of cystic fibrosis (CF) is frequently complicated by

acute pulmonary exacerbations, superimposed on a gradual decline in pulmonary
function. Mechanisms include:
• Bacteria – Bacteria play an important but somewhat ill-defined role in the

pathophysiology of pulmonary exacerbations. Key bacterial pathogens are
discussed separately ( table 1). (See 'Bacteria' above and "Cystic fibrosis: Antibiotic
therapy for chronic pulmonary infection", section on 'Pathogens'.)
• Viruses – Viral pathogens frequently play a role in initiating exacerbations and may
be important contributors to declining pulmonary function. Influenza is an
important vaccine-preventable pathogen. (See 'Viruses' above.)
● Treatment
• Antibiotics – Treatment of exacerbations with systemic antibiotics is a mainstay of

CF care. Selection and dosing of antibiotics are summarized in the table ( table 2)
and discussed separately. (See "Cystic fibrosis: Antibiotic therapy for pulmonary
exacerbations".)

• Continuation of the chronic treatment regimen – The patient's chronic treatment

regimen should be continued or intensified during an acute exacerbation, including
CF transmembrane modulator (CFTR) therapy, airway clearance therapies,
optimization of nutrition, and management of CF-related diabetes (if present). (See
'Continuation of the chronic treatment regimen' above.)
The role for inhaled antibiotics during pulmonary exacerbations is uncertain. (See
"Cystic fibrosis: Antibiotic therapy for pulmonary exacerbations", section on
'Managing the chronically prescribed antibiotics'.)
• Antiviral agents – Antiviral treatment is indicated for people with CF with known or
suspected influenza because they are at high risk for severe or complicated disease.
Indications and regimens are discussed separately. (See "Seasonal influenza in
children: Management", section on 'Antiviral therapy' and "Seasonal influenza in
nonpregnant adults: Treatment".)
• Other medications – We use bronchodilators as pretreatment for airway clearance

therapies and to treat asthma-like symptoms. We use glucocorticoids only for the
small subset of patients with asthma-like symptoms, although practice varies. (See
'Bronchodilators' above and 'Glucocorticoids' above.)
● Respiratory support – People with respiratory failure or complications (hemoptysis,

pneumothorax) are candidates for respiratory support during a pulmonary
exacerbation, including supplemental oxygen, noninvasive ventilation, invasive
ventilation, or extracorporeal membrane oxygenation support (ECMO). (See
'Respiratory support' above.)
An episode of respiratory failure should prompt discussion of end-of-life care, quality of

life, and possible indications for lung transplantation. Advanced CF lung disease is not a
contraindication to intensive care unit (ICU) admission or mechanical ventilation,
regardless of the patient's lung transplant status. (See 'Intensive care unit treatment'
above.)
● Prognosis – Following a pulmonary exacerbation, the recovery of lost forced expiratory

volume in one second (FEV1) is often incomplete. Pulmonary exacerbations are
associated with accelerated loss of lung function, decreased quality of life, and
increased mortality. Thus, reducing the frequency and optimizing treatment of
exacerbations is an important goal of CF care. (See 'Prognosis' above.)
Use of UpToDate is subject to the Terms of Use.
REFERENCES

1. Rommens JM, Iannuzzi MC, Kerem B, et al. Identification of the cystic fibrosis gene:
chromosome walking and jumping. Science 1989; 245:1059.
2. Shteinberg M, Haq IJ, Polineni D, Davies JC. Cystic fibrosis. Lancet 2021; 397:2195.
3. Cystic Fibrosis Foundation. 2022 Cystic Fibrosis Foundation Patient Registry Highlights. 2
023. Available at: https://www.cff.org/media/29691/download (Accessed on October 30,
2023).
4. Mayer-Hamblett N, Rosenfeld M, Emerson J, et al. Developing cystic fibrosis lung
transplant referral criteria using predictors of 2-year mortality. Am J Respir Crit Care Med
2002; 166:1550.
5. Liou TG, Adler FR, Fitzsimmons SC, et al. Predictive 5-year survivorship model of cystic
fibrosis. Am J Epidemiol 2001; 153:345.
6. Britto MT, Kotagal UR, Hornung RW, et al. Impact of recent pulmonary exacerbations on
quality of life in patients with cystic fibrosis. Chest 2002; 121:64.
7. Konstan MW, Morgan WJ, Butler SM, et al. Risk factors for rate of decline in forced
expiratory volume in one second in children and adolescents with cystic fibrosis. J
Pediatr 2007; 151:134.
8. Caverly LJ, VanDevanter DR. The Elusive Role of Airway Infection in Cystic Fibrosis
Exacerbation. J Pediatric Infect Dis Soc 2022; 11:S40.
9. Wagener JS, Rasouliyan L, VanDevanter DR, et al. Oral, inhaled, and intravenous
antibiotic choice for treating pulmonary exacerbations in cystic fibrosis. Pediatr
Pulmonol 2013; 48:666.
10. West NE, Beckett VV, Jain R, et al. Standardized Treatment of Pulmonary Exacerbations
(STOP) study: Physician treatment practices and outcomes for individuals with cystic
fibrosis with pulmonary Exacerbations. J Cyst Fibros 2017; 16:600.
11. Cogen JD, Oron AP, Gibson RL, et al. Characterization of Inpatient Cystic Fibrosis
Pulmonary Exacerbations. Pediatrics 2017; 139.
12. Kraynack NC, Gothard MD, Falletta LM, McBride JT. Approach to treating cystic fibrosis
pulmonary exacerbations varies widely across US CF care centers. Pediatr Pulmonol
2011; 46:870.
13. Flume PA, Mogayzel PJ Jr, Robinson KA, et al. Cystic fibrosis pulmonary guidelines:
treatment of pulmonary exacerbations. Am J Respir Crit Care Med 2009; 180:802.
14. Cystic Fibrosis Trust. Standards for the Clinical Care of Children and Adults with cystic fib
rosis in the UK. 2nd ed. 2011. Available at: https://www.cysticfibrosis.org.uk/sites/defaul
t/files/2022-10/Standards%20of%20care_interim%202022.pdf (Accessed on January 16, 2
023).

15. Smyth AR, Bell SC, Bojcin S, et al. European Cystic Fibrosis Society Standards of Care:
Best Practice guidelines. J Cyst Fibros 2014; 13 Suppl 1:S23.
16. Cystic Fibrosis: Diagnosis and management, National Guideline Alliance (UK). (Ed), Natio
nal Institute for Health and Care Excellence (NICE), London 2017.
17. Sanders DB, Bittner RC, Rosenfeld M, et al. Pulmonary exacerbations are associated with
subsequent FEV1 decline in both adults and children with cystic fibrosis. Pediatr
Pulmonol 2011; 46:393.
18. Waters V, Stanojevic S, Atenafu EG, et al. Effect of pulmonary exacerbations on long-
term lung function decline in cystic fibrosis. Eur Respir J 2012; 40:61.
19. Wagener JS, Williams MJ, Millar SJ, et al. Pulmonary exacerbations and acute declines in
lung function in patients with cystic fibrosis. J Cyst Fibros 2018; 17:496.
20. VanDevanter DR, Hamblett NM, Simon N, et al. Evaluating assumptions of definition-
based pulmonary exacerbation endpoints in cystic fibrosis clinical trials. J Cyst Fibros
2021; 20:39.
21. Goss CH, Heltshe SL, West NE, et al. A Randomized Clinical Trial of Antimicrobial
Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment. Am J Respir Crit Care
Med 2021; 204:1295.
22. Carter SC, Franciosi AN, O'Shea KM, et al. Acute Pulmonary Exacerbation Phenotypes in
Patients with Cystic Fibrosis. Ann Am Thorac Soc 2022; 19:1818.
23. Dong K, Huh SM, Lam GY, et al. Pulmonary exacerbation inflammatory phenotypes in
adults with cystic fibrosis. J Cyst Fibros 2023; 22:306.
24. Bilton D, Canny G, Conway S, et al. Pulmonary exacerbation: towards a definition for use
in clinical trials. Report from the EuroCareCF Working Group on outcome parameters in
clinical trials. J Cyst Fibros 2011; 10 Suppl 2:S79.
25. Bouzek DC, Ren CL, Thompson M, et al. Evaluating FEV1 decline in diagnosis and
management of pulmonary exacerbations in children with cystic fibrosis. Pediatr
Pulmonol 2022; 57:1709.
26. Lechtzin N, Mayer-Hamblett N, West NE, et al. Home Monitoring of Patients with Cystic
Fibrosis to Identify and Treat Acute Pulmonary Exacerbations. eICE Study Results. Am J
Respir Crit Care Med 2017; 196:1144.
27. Schechter MS, Schmidt HJ, Williams R, et al. Impact of a program ensuring consistent
response to acute drops in lung function in children with cystic fibrosis. J Cyst Fibros
2018; 17:769.
28. Anstead M, Saiman L, Mayer-Hamblett N, et al. Pulmonary exacerbations in CF patients

with early lung disease. J Cyst Fibros 2014; 13:74.

29. Stanojevic S, McDonald A, Waters V, et al. Effect of pulmonary exacerbations treated with
oral antibiotics on clinical outcomes in cystic fibrosis. Thorax 2017; 72:327.
30. Goss CH, Burns JL. Exacerbations in cystic fibrosis. 1: Epidemiology and pathogenesis.
Thorax 2007; 62:360.
31. Patel S, Thompson MD, Slaven JE, et al. Reduction of pulmonary exacerbations in young
children with cystic fibrosis during the COVID-19 pandemic. Pediatr Pulmonol 2021;
56:1271.
32. VanDevanter DR, Morris NJ, Konstan MW. IV-treated pulmonary exacerbations in the
prior year: An important independent risk factor for future pulmonary exacerbation in
cystic fibrosis. J Cyst Fibros 2016; 15:372.
33. Quittner AL, Zhang J, Marynchenko M, et al. Pulmonary medication adherence and
health-care use in cystic fibrosis. Chest 2014; 146:142.
34. Schechter MS, Ostrenga JS, Fink AK, et al. Decreased survival in cystic fibrosis patients
with a positive screen for depression. J Cyst Fibros 2021; 20:120.
35. Asner S, Waters V, Solomon M, et al. Role of respiratory viruses in pulmonary
exacerbations in children with cystic fibrosis. J Cyst Fibros 2012; 11:433.
36. Gonzalez-Rosales N, Kasi AS, McCracken CE, et al. Impact of viral respiratory infections
on pulmonary exacerbations in children with cystic fibrosis. Pediatr Pulmonol 2023;
58:871.
37. Goffard A, Lambert V, Salleron J, et al. Virus and cystic fibrosis: rhinoviruses are
associated with exacerbations in adult patients. J Clin Virol 2014; 60:147.
38. Etherington C, Naseer R, Conway SP, et al. The role of respiratory viruses in adult
patients with cystic fibrosis receiving intravenous antibiotics for a pulmonary
exacerbation. J Cyst Fibros 2014; 13:49.
39. Chin M, De Zoysa M, Slinger R, et al. Acute effects of viral respiratory tract infections on
sputum bacterial density during CF pulmonary exacerbations. J Cyst Fibros 2015; 14:482.
40. Muhlebach MS, Hatch JE, Einarsson GG, et al. Anaerobic bacteria cultured from cystic
fibrosis airways correlate to milder disease: a multisite study. Eur Respir J 2018; 52.
41. Carmody LA, Caverly LJ, Foster BK, et al. Fluctuations in airway bacterial communities
associated with clinical states and disease stages in cystic fibrosis. PLoS One 2018;
13:e0194060.
42. Castner LM, Zimbric M, Cahalan S, et al. Outcomes of cystic fibrosis pulmonary
exacerbations treated with antibiotics with activity against anaerobic bacteria. J Cyst
Fibros 2021; 20:926.
43. Huang YJ, LiPuma JJ. The Microbiome in Cystic Fibrosis. Clin Chest Med 2016; 37:59.

44. Hurley MN, Prayle AP, Flume P. Intravenous antibiotics for pulmonary exacerbations in
people with cystic fibrosis. Cochrane Database Syst Rev 2015; :CD009730.
45. Shoki AH, Mayer-Hamblett N, Wilcox PG, et al. Systematic review of blood biomarkers in
cystic fibrosis pulmonary exacerbations. Chest 2013; 144:1659.
46. Ratjen F, Waters V, Klingel M, et al. Changes in airway inflammation during pulmonary
exacerbations in patients with cystic fibrosis and primary ciliary dyskinesia. Eur Respir J
2016; 47:829.
47. Ordoñez CL, Henig NR, Mayer-Hamblett N, et al. Inflammatory and microbiologic
markers in induced sputum after intravenous antibiotics in cystic fibrosis. Am J Respir
Crit Care Med 2003; 168:1471.
48. Esther CR Jr, Muhlebach MS, Ehre C, et al. Mucus accumulation in the lungs precedes
structural changes and infection in children with cystic fibrosis. Sci Transl Med 2019; 11.
49. Sanders DB, Khan U, Heltshe SL, et al. Association of site of treatment with clinical
outcomes following intravenous antimicrobial treatment of a pulmonary exacerbation. J
Cyst Fibros 2022; 21:574.
50. Schechter MS, VanDevanter DR, Pasta DJ, et al. Treatment Setting and Outcomes of
Cystic Fibrosis Pulmonary Exacerbations. Ann Am Thorac Soc 2018; 15:225.
51. Balaguer A, González de Dios J. Home versus hospital intravenous antibiotic therapy for
cystic fibrosis. Cochrane Database Syst Rev 2015; :CD001917.
52. Wolter JM, Bowler SD, Nolan PJ, McCormack JG. Home intravenous therapy in cystic
fibrosis: a prospective randomized trial examining clinical, quality of life and cost
aspects. Eur Respir J 1997; 10:896.
53. Collaco JM, Green DM, Cutting GR, et al. Location and duration of treatment of cystic
fibrosis respiratory exacerbations do not affect outcomes. Am J Respir Crit Care Med
2010; 182:1137.
54. Davis PB, di Sant'Agnese PA. Assisted ventilation for patients with cystic fibrosis. JAMA
1978; 239:1851.
55. Smith MA, McGarry ME, Ly NP, Zinter MS. Outcomes of Children With Cystic Fibrosis
Admitted to PICUs. Pediatr Crit Care Med 2020; 21:e879.
56. Oud L. Critical illness among adults with cystic fibrosis in Texas, 2004-2013: Patterns of
ICU utilization, characteristics, and outcomes. PLoS One 2017; 12:e0186770.
57. Kapnadak SG, Dimango E, Hadjiliadis D, et al. Cystic Fibrosis Foundation consensus
guidelines for the care of individuals with advanced cystic fibrosis lung disease. J Cyst
Fibros 2020; 19:344.
58. Pollak M, Shaw M, Wilson D, et al. Bronchodilator responsiveness in cystic fibrosis
children treated for pulmonary exacerbations. Pediatr Pulmonol 2021; 56:2036.

59. Hordvik NL, Sammut PH, Judy CG, et al. The effects of albuterol on the lung function of
hospitalized patients with cystic fibrosis. Am J Respir Crit Care Med 1996; 154:156.
60. Hester KL, Powell T, Downey DG, et al. Glucocorticoids as an adjuvant treatment to
intravenous antibiotics for cystic fibrosis pulmonary exacerbations: a UK Survey. J Cyst
Fibros 2007; 6:311.
61. Dovey M, Aitken ML, Emerson J, et al. Oral corticosteroid therapy in cystic fibrosis
patients hospitalized for pulmonary exacerbation: a pilot study. Chest 2007; 132:1212.
62. Muirhead CA, Lanocha N, Markwardt S, MacDonald KD. Evaluation of rescue oral
glucocorticoid therapy during inpatient cystic fibrosis exacerbations. Pediatr Pulmonol
2021; 56:891.
63. Davis CS, Faino AV, Onchiri F, et al. Systemic Corticosteroids in the Management of
Pediatric Cystic Fibrosis Pulmonary Exacerbations. Ann Am Thorac Soc 2023; 20:75.
64. Centers for Disease Control and Prevention. Influenza Antiviral Medications: Summary f
or Clinicians. 2022. Available at: https://www.cdc.gov/flu/professionals/antivirals/summa
ry-clinicians.htm (Accessed on January 09, 2023).
65. Hong E, Almond LM, Chung PS, et al. Physiologically-Based Pharmacokinetic-Led
Guidance for Patients With Cystic Fibrosis Taking Elexacaftor-Tezacaftor-Ivacaftor With
Nirmatrelvir-Ritonavir for the Treatment of COVID-19. Clin Pharmacol Ther 2022;
111:1324.
66. Dwyer TJ, Robbins L, Kelly P, et al. Non-invasive ventilation used as an adjunct to airway
clearance treatments improves lung function during an acute exacerbation of cystic
fibrosis: a randomised trial. J Physiother 2015; 61:142.
67. Schechter MA, Ganapathi AM, Englum BR, et al. Spontaneously Breathing Extracorporeal
Membrane Oxygenation Support Provides the Optimal Bridge to Lung Transplantation.
Transplantation 2016; 100:2699.
68. Biscotti M, Gannon WD, Agerstrand C, et al. Awake Extracorporeal Membrane
Oxygenation as Bridge to Lung Transplantation: A 9-Year Experience. Ann Thorac Surg
2017; 104:412.
69. Heltshe SL, Goss CH, Thompson V, et al. Short-term and long-term response to
pulmonary exacerbation treatment in cystic fibrosis. Thorax 2016; 71:223.
70. Sanders DB, Bittner RC, Rosenfeld M, et al. Failure to recover to baseline pulmonary
function after cystic fibrosis pulmonary exacerbation. Am J Respir Crit Care Med 2010;
182:627.
71. Gold LS, Patrick DL, Hansen RN, et al. Correspondence between lung function and
symptom measures from the Cystic Fibrosis Respiratory Symptom Diary-Chronic
Respiratory Infection Symptom Score (CFRSD-CRISS). J Cyst Fibros 2019; 18:886.

72. Sequeiros IM, Jarad NA. Extending the course of intravenous antibiotics in adult patients
with cystic fibrosis with acute pulmonary exacerbations. Chron Respir Dis 2012; 9:213.
Topic 110933 Version 35.0

GRAPHICS
Median predicted survival of patients with cystic fibrosis
This chart depicts the birth year on the x-axis and median predicted survival for that birth cohort on
the y-axis. The median predicted survival for a given birth year is the age at which one-half of the
those born that year are predicted to survive beyond, given the age distribution of deaths that
occurred during that specific year and assuming no future changes in mortality rate. Statistics from
1940 to 1978 are collected from Davis et al [1] . Statistics from 1990 to 2022 are collected from the
Cystic Fibrosis Foundation Patient Registry [2] .
Data from:
1. Davis PB, Drumm M, Konstan MW. Cystic fibrosis. Am J Respir Crit Care Med 1996; 154:1229.
2. 2022 Patient Registry Annual Data Report. Cystic Fibrosis Foundation. https://www.cff.org/medical-
professionals/patient-registry (Accessed on November 8, 2023).
Graphic 61930 Version 18.0

Prevalence of bacteria identified in respiratory secretions from patients with

cystic fibrosis, by age cohort
The graph shows the proportion of individuals in various age groups who had positive cultures for
each of these bacterial species during 2019. We did not include data from the 2020 and 2021 Cystic
Fibrosis Foundation Patient Registry reports, which may be misleading because many fewer cultures
were collected during that period due to the COVID-19 pandemic.
P. aeruginosa: Pseudomonas aeruginosa; H. influenza: Haemophilus influenza; B. cepacia complex:

Burkholderia cepacia complex; S. aureus: Staphylococcus aureus; MRSA: methicillin-resistant S. aureus;
Achromobacter: Achromobacter xylosoxidans; S. maltophilia: Stenotrophomonas maltophilia; MDR-PA:
multidrug-resistant P. aeruginosa; COVID-19: coronavirus disease 2019.
Reproduced with permission from: Cystic Fibrosis Foundation Patient Registry: 2019 Annual Data Report, Bethesda, MD.
Copyright © 2020 Cystic Fibrosis Foundation.

Microorganisms isolated from respiratory secretions of patients with cystic

fibrosis, all ages
Organism Percent with positive respiratory

cultures
Staphylococcus aureus 60.8%
Methicillin-resistant S. aureus (MRSA) 15.6%
Pseudomonas aeruginosa 26.0%
Multidrug-resistant P. aeruginosa (MDR-PA) 3.3%
Stenotrophomonas maltophilia 5.0%
Burkholderia cepacia complex 1.3%
Achromobacter (Alcaligenes) xylosoxidans 2.4%
Nontuberculous mycobacteria (NTM) 10.3%*
* For NTM, this represents the percentage of patients with 1 or more mycobacterial species isolated
among those who had at least 1 mycobacterial culture performed during 2022.
Data from: 2022 Patient Registry Annual Data Report. Cystic Fibrosis Foundation. https://www.cff.org/medical-
professionals/patient-registry (Accessed January 8, 2024).

Antibiotics for treating exacerbations of cystic fibrosis lung disease
Pediatric
Bacteria Antibiotic Adult dose Comme
dose*
Staphylococcus aureus Cefazolin 100 mg/kg 1.5 g every 6 Maximum 6

(methicillin-sensitive) per day in 3 hours or 2 g day.
or 4 divided every 8
doses hours
OR
Nafcillin 100 to 200 2 g every 4 to Maximum 12

mg/kg per 6 hours day.
day in 4 or 6
divided
doses
Oral regimens (for mild exacerbations) ¶
One of the following, guided by susceptibility testing:

Trimethoprim-sulfamethoxazole Δ
Doxycycline
Amoxicillin-clavulanate
S. aureus Vancomycin ◊ 60 mg/kg per 45 to 60 Maximum 3.

(methicillin-resistant) [1] day in 3 (or mg/kg per per day for
4) divided day in 3 children and
doses divided per day for a
doses
These doses
for patients w
normal rena
function. Do
frequency ar
adjusted bas
serum vanco
concentratio
using either
trough-direc
AUC-guided
dosing § . To r
the risk of re
toxicity, a be
lactam other
piperacillin-
tazobactam
be selected w
being used i
combination

vancomycin
tobramycin [2
OR
Linezolid Children <12 600 mg Risk of

years: intravenously myelosuppre
30 mg/kg per or orally (most comm
day every 12 thrombocyto
intravenously hours with treatme
or orally in 3 days or whe
divided insufficiency
doses present [3] .
Children ≥12
years:
Use adult
dose
OR
Ceftaroline 45 mg/kg per 600 mg Maximum 18

day intravenously mg per day.
intravenously every 8
in 3 divided hours
doses
Oral regimens ¶
One of the following, guided by susceptibility testing:

Trimethoprim-sulfamethoxazole Δ (for mild exacerbations)
Doxycycline (for mild exacerbations)
Linezolid (for moderate or severe exacerbations)
Pseudomonas One of the following:

aeruginosa
Piperacillin-tazobactam ¥ ‡ 350 to 4.5 g every 6 Maximum 16
450 mg/kg † hours per day.
per day in 4
divided
doses
Ceftazidime ¥ 150 to 200 2 g every 6 to Maximum 8

mg/kg per 8 hours day.
day in 3 or 4
divided
doses
Cefepime 150 mg/kg 2 g every 8 Maximum 6

per day in 3 hours day.
divided
doses

Imipenem-cilastatin 60 to 100 0.5 to 1 g Maximum 4

mg/kg per every 6 day.
day in 4 hours
divided
doses
Meropenem 120 mg/kg 2 g every 8 Maximum 6

per day in 3 hours day.
divided
doses
Ticarcillin-clavulanate ¥ ‡ 400 mg/kg** 3.1 g every 4 Maximum 18

per day in 4 to 6 hours per day.
or 6 divided
doses
PLUS
Ciprofloxacin Oral dose: Oral dose: Maximum do

40 mg/kg per 750 mg every Oral do
day in 2 12 hours per day
divided childre
Intravenous
doses g per d
dose:
Intravenous 400 mg every adults
dose: 8 to 12 hours Intraven
30 mg/kg per dose: 1.
day in 3 per day
divided Can be used
doses preference t
aminoglycos
colistin due t
toxicity,
particularly w
Pseudomona
sensitive.
OR
Levofloxacin Oral and Oral and Maximum do

intravenous intravenous Oral an
dose: dose: intraven
6 750 mg dose: 75
months every per day
to 4 24
Can be used
years hours
preference t
old: 16
aminoglycos
to 20
colistin due t
mg/kg
toxicity,
per day
particularly w
in 2
in vitro testin
divided
demonstrate
doses
5 to 16 the P. aerugin
years sensitive to
old: 8 to levofloxacin.
10
mg/kg
per day
every
24
hours
OR
Tobramycin ¶¶ 10 mg/kg 10 mg/kg Refer to the

every 24 every 24 UpToDate to
hours hours treatment of
(adjust dose (adjust dose pulmonary
for for exacerbation
overweight overweight a discussion
patients) ΔΔ patients) ΔΔ serum
concentratio
monitoring f
aminoglycos
OR and for dose
interval
Amikacin ¶¶ 30 to 35 30 to 35 adjustment f
mg/kg every mg/kg every renal insuffic
24 hours 24 hours Dose and
(adjust dose (adjust dose frequency fr
for for previous cou
overweight overweight that achieve
patients) ΔΔ patients) ΔΔ therapeutic r
may be cons
for determin
the initial do
OR
Colistin (colistimethate 2.5 to 2.5 to Maximum 30

sodium) 5 mg/kg ◊◊ 5 mg/kg ◊◊ per day (coli
(colistin base (colistin-base base activity
activity §§ ) activity §§ )
Colistin is a
per day in 3 per day in 3
second-line d
divided divided
that may be
doses doses
when the P.
aeruginosa
demonstrate
vitro resistan
all
aminoglycos
or when the
patient fails

improve on a
aminoglycos
containing
regimen.
IMPORTANT
units and
recommend
dosing regim
vary by prod
and country.
shown here
specific to U
States-licens
information
Coly-Mycin M
which labels
product as u
"colistin-base
activity" §§ . C
local official
product
information
details befor
using this ag
Adverse effe
include rena
neurotoxiciti
S. aureus (methicillin- Same antibiotics shown above for P. aeruginosa alone EXCEPT that ceftazidim
sensitive) should not be used, because of poor activity against S. aureus.
AND P. aeruginosa
S. aureus (methicillin- Same antibiotics shown above for P. aeruginosa alone.

resistant)
PLUS one of the following (3 antibiotics total):
AND P. aeruginosa
Vancomycin ◊ 60 mg/kg per 45 to 60 Maximum 3.
day in 3 (or mg/kg per per day for
4) divided day in 3 children and
doses divided per day for a
doses
These doses
for patients w
normal rena
function. Do
frequency ar
adjusted bas
serum vanco
concentratio
using either
trough-direc
AUC-guided

dosing § . To r
the risk of re
toxicity, a be
lactam other
piperacillin-
tazobactam
be selected w
being used i
combination
vancomycin
tobramycin [2
OR
Linezolid Children <12 600 mg Risk of

years: intravenously myelosuppre
30 mg/kg per or orally (most comm
day every 12 thrombocyto
intravenously hours with treatme
or orally in 3 days or whe
divided insufficiency
doses present [3] .
Children ≥12
years:
Use adult
dose
The table contains recommended choices of antibiotics based on the type of bacteria isolated. The
selection should be modified based on results of sensitivity testing and renal function. The doses
given here are typical for patients with cystic fibrosis. Higher and/or more frequent dosing of some
antibiotics is often required for cystic fibrosis patients as compared with patients without cystic
fibrosis, and a wider range of dose requirements is to be expected. Note that these dosing
recommendations do not apply to cystic fibrosis patients who have undergone lung transplantation.
For most of these antibiotics, dosing reflects recommendations from a comprehensive review of
antipseudomonal antibiotics in cystic fibrosis [4] . For a few of the antibiotics (piperacillin-tazobactam,
ticarcillin-clavulanate, and ceftazidime), the review recommends much higher doses for cystic fibrosis
patients than are used for patients without cystic fibrosis. These are based primarily on
pharmacokinetic and pharmacodynamic considerations, but clinical trial data for these very high
doses are lacking. Therefore, we suggest intermediate doses for these drugs, as shown in the table
above. Many clinicians are prescribing beta-lactam antibiotics to be administered by prolonged or
continuous infusion, based on a strong theoretical basis and pharmacokinetic analysis of drug levels
in patients with cystic fibrosis.
MSSA: methicillin-sensitive S. aureus; AUC: area under the time-concentration curve; MIC: minimum
inhibitory concentration.
* The dose given to children generally should not exceed the dose for adults.
¶ The severity of an exacerbation is typically based upon changes in clinical symptoms and pulmonary
function tests compared with the patient's own baseline.

Δ For trimethoprim-sulfamethoxazole, dosing for patients with cystic fibrosis may need to be higher
than that recommended for non-cystic fibrosis patients (refer to the UpToDate topic on treatment of
acute pulmonary exacerbations in cystic fibrosis).
◊ For vancomycin, some clinicians target a lower serum trough level of 10 to 15 mg/mL since this
reduces the risk for nephrotoxicity, and pharmacokinetic/pharmacodynamic studies showed that this
approach achieves the desired target of AUC/MIC ≥400 in children and adolescents [5] .
§ For therapeutic monitoring of vancomycin, either trough-directed or AUC-guided strategies may be

used. AUC-guided dosing requires support from a clinical pharmacist, and was endorsed by a
consensus guideline. [5] Refer to UpToDate content on treatment of pulmonary exacerbations in cystic
fibrosis.
¥ For piperacillin-tazobactam, ticarcillin-clavulanate, and ceftazidime, higher doses than those shown
may be considered on a case-by-case basis to optimize pharmacodynamic targets in patients with
multidrug-resistant pathogens and poor clinical response to initial treatment [4] . Many clinicians are
prescribing beta-lactam antibiotics to be administered by prolonged or continuous infusion, based on
a strong theoretical basis and pharmacokinetic analysis of drug levels. Ticarcillin-clavulanate is no
longer available in North America, Australia, the United Kingdom, and most of Europe.
‡ For treatment of P. aeruginosa without MSSA, piperacillin without tazobactam or ticarcillin without
clavulanate can be used where available (in combination with ciprofloxacin, an aminoglycoside, or
colistin, depending on reported susceptibilities).
† Of piperacillin component. Doses >600 mg/kg/day may be considered on a case-by-case basis, but
increased risk of toxicity is expected, including serum sickness, anemias, and bone marrow
suppression.
** Of ticarcillin component.
¶¶ Monitor aminoglycoside blood levels and creatinine to ensure efficacy and avoid toxicity. The dose
and frequency from a previous course of treatment may be used initially if serum concentrations were
in the target range and if creatinine clearance is not substantially changed, but drug levels should still
be monitored.
ΔΔ For patients with total body weight greater than 120% of ideal body weight, initial dose selection
should be based on adjusted body weight or dosing weight. A calculator for ideal body weight and
dosing weight in adults is available in UpToDate.
◊◊ If the patient is overweight, the initial dose of colistin should be based on ideal body weight. A
calculator for ideal body weight in adults is available in UpToDate.
§§ For an explanation of our recommended colistin dosing for people with cystic fibrosis, refer to the
UpToDate content on antibiotic therapy in cystic fibrosis. Conversions: 1 mg colistin-base activity
(CBA; United States product) = 30,000 international units of colistimethate sodium (CMS; European
Union product).
References:
1. Epps QJ, Epps KL, Young DC, et al. State of the art in cystic fibrosis pharmacology optimization of antimicrobials in the
treatment of cystic fibrosis pulmonary exacerbations: III. Executive summary. Pediatr Pulmonol 2021; 56:1825.
2. LeCleir LK, Pettit RS. Piperacillin-tazobactam versus cefepime incidence of acute kidney injury in combination with
vancomycin and tobramycin in pediatric cystic fibrosis patients. Pediatr Pulmonol 2017; 52:1000.
3. Hiraki Y, Tsuji Y, Matsumoto K, et al. Influence of linezolid clearance on the induction of thrombocytopenia and
reduction of hemoglobin. Am J Med Sci 2011; 342:456.
4. Zobell JT, Young DC, Waters CD, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary
exacerbations: VI. Executive Summary. Pediatr Pulmonol 2013; 48:525.

5. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus
aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the
Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases
Pharmacists. Am J Health Syst Pharm 2020; 77:835.
Many but not all of the dosing recommendations in this table are reflected in the following source: Zobell JT, Young DC, Waters
CD, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: VI. Executive Summary.
Pediatr Pulmonol 2013; 48:525.

Contributor Disclosures
Richard H Simon, MD No relevant financial relationship(s) with ineligible companies to
disclose. James F Chmiel, MD, MPH Grant/Research/Clinical Trial Support: Cystic Fibrosis Foundation
[Cystic fibrosis]; National Institutes of Health [Asthma; cystic fibrosis]; Vertex [Cystic fibrosis].
Consultant/Advisory Boards: Cystic Fibrosis Foundation [Cystic fibrosis]; Microbion [Cystic fibrosis];
Phylaxis [Cystic fibrosis]. Other Financial Interest: American Board of Pediatrics [Honorarium received
for service on credentialing committee]; American Thoracic Society [Course Director for Fellows Track
Symposium]; Cystic Fibrosis Foundation [Honorarium received for service on clinical research
committee]. All of the relevant financial relationships listed have been mitigated. Alison G Hoppin,
MD No relevant financial relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

Cystic Fibrosis - Management of Pulmonary Exacerbations - UpToDate

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Cystic Fibrosis - Management of Pulmonary Exacerbations - UpToDate

Uploaded by

Copyright:

Available Formats

20/1/24, 22:55 Cystic fibrosis: Management of pulmonary exacerbations - UpToDate

Official reprint from UpToDate®

Cystic fibrosis: Management of pulmonary

Literature review current through: Dec 2023.

Treatment of pulmonary exacerbations in CF is multifaceted, involving antibiotics, chest

https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&so… 1/31

Other aspects of pulmonary disease in CF are discussed in separate topic reviews:

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

● (See "Cystic fibrosis: Treatment with CFTR modulators".)

● (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection".)

● (See "Cystic fibrosis: Clinical manifestations of pulmonary disease".)

● (See "Cystic fibrosis: Management of advanced lung disease".)

PULMONARY EXACERBATIONS IN CYSTIC FIBROSIS

Diagnosis — In clinical practice, a pulmonary exacerbation is diagnosed based on changes

• New or increased cough

https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&so… 2/31

● Pulmonary function tests – Reductions in pulmonary function as measured by forced

● In an individual with mild pulmonary disease at baseline, an exacerbation is considered

● In an individual with severe pulmonary disease at baseline, an exacerbation is

https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&so… 3/31

the highly effective CF transmembrane conductance regulator (CFTR) modulator elexacaftor-

Important pathogens include ( table 1):

https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&so… 4/31

Although bacteria are clearly involved in the pathophysiology of pulmonary exacerbations in

Inflammation — The CF airway is characterized by chronic neutrophil-rich inflammation (see

Severe pulmonary exacerbations usually require hospitalization to adequately manage the

Home management of exacerbations

● Mild exacerbations – Most mild exacerbations can be managed in an outpatient

● Moderate exacerbations – Moderate or severe pulmonary exacerbations are often

https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&so… 5/31

● Respiratory insufficiency requiring respiratory support (see 'Respiratory support' below)

https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&so… 6/31

Antibiotics — Treatment of exacerbations with systemic antibiotics is a mainstay of CF care

Continuation of the chronic treatment regimen — The patient's chronic treatment

Key components include:

● CF transmembrane conductance regulator (CFTR) modulators. (See "Cystic fibrosis:

● Antiinflammatory medications (eg, azithromycin, ibuprofen) in selected patients.

pulmonary exacerbations", section on 'Managing the chronically prescribed antibiotics'

● Optimization of nutritional status. (See "Cystic fibrosis: Nutritional issues", section on

Other medications (for selected patients)

Bronchodilators — During pulmonary exacerbations, our practice is to administer short-

● Prior to airway clearance therapy and exercise

Evidence supporting routine use of bronchodilators during pulmonary exacerbations is

https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&so… 8/31

studies have evaluated more prolonged effects of bronchodilators on pulmonary

Glucocorticoids — There is considerable variation in practice regarding use of

Our practice is to administer a course of prednisone (2 mg/kg/day [maximum 60 mg daily]

Another strategy used by some clinicians is to administer systemic glucocorticoids to

https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&so… 9/31

● COVID-19 – CF is a condition associated with a higher risk of developing severe COVID-

● Supplemental oxygen – We administer supplemental oxygen as needed during

● Noninvasive ventilation – We offer noninvasive positive pressure ventilation to

pulmonary exacerbation [66]. There was no significant increased rate of improvement

● Extracorporeal membrane oxygenation support (ECMO) – When adequate

https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&s… 11/31

Given the adverse consequences of exacerbations, reducing exacerbation frequency is an

SOCIETY GUIDELINE LINKS

SUMMARY AND RECOMMENDATIONS

● Definition – In clinical practice, a pulmonary exacerbation is diagnosed based on a

● Pathogenesis – The clinical course of cystic fibrosis (CF) is frequently complicated by

• Bacteria – Bacteria play an important but somewhat ill-defined role in the

• Antibiotics – Treatment of exacerbations with systemic antibiotics is a mainstay of

https://www.uptodate.com/contents/cystic-fibrosis-management-of-pulmonary-exacerbations/print?search=ciprofloxacina en fibrosis quistica&s… 12/31