Pseudomonas Aeruginosa Pneumonia

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Pseudomonas aeruginosa pneumonia

AUTHOR: Souha S Kanj, MD
SECTION EDITOR: Stephen B Calderwood, MD
DEPUTY EDITOR: Keri K Hall, MD, MS
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2024.

This topic last updated: Dec 08, 2023.
INTRODUCTION
Pseudomonas aeruginosa is one of the most important and most commonly considered
pathogens in the differential diagnosis of gram-negative infections. Consideration of this
organism is important because it causes severe hospital-acquired infections, especially in
immunocompromised hosts, is often antibiotic resistant, complicating the choice of therapy,
and is associated with a high mortality rate.
The clinical manifestations, diagnosis, and treatment of P. aeruginosa pneumonia will be

reviewed here.
The general principles of antimicrobial treatment of infections caused by P. aeruginosa,

including antibiotic options and decisions on combination therapy, are discussed in detail
elsewhere. (See "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections".)
The clinical manifestations and management of other P. aeruginosa infections and the
epidemiology and pathogenesis of infection with this organism are also discussed
separately.
● (See "Epidemiology, microbiology, and pathogenesis of Pseudomonas aeruginosa

infection".)
● (See "Pseudomonas aeruginosa bacteremia and endocarditis".)
● (See "Pseudomonas aeruginosa skin and soft tissue infections".)
● (See "Pseudomonas aeruginosa infections of the eye, ear, urinary tract, gastrointestinal
tract, and central nervous system".)
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● (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on
'Pseudomonas aeruginosa' and "Cystic fibrosis: Antibiotic therapy for pulmonary
exacerbations".)
EPIDEMIOLOGY
Hospital-acquired pneumonia — P. aeruginosa is a common cause of gram-negative

hospital-acquired (nosocomial) pneumonia [1-6]. This was illustrated in a prospective series
of 556 patients in which P. aeruginosa was the most common gram-negative pathogen
implicated in both hospital-acquired and ventilator-associated pneumonia (VAP) [1]. In a
large multicenter survey of gram-negative aerobic bacteria isolated from patients in
intensive care units (ICUs) in the US, P. aeruginosa was the most commonly isolated gram-
negative aerobic bacterium (23 percent) and was the most common bacterium recurrently
isolated from the respiratory tract (32 percent) [7]. Hospital-acquired pneumonia (HAP) can
occur via aspiration of endogenous oral flora or via aspiration of organisms from
contamination of ventilator tubing or other health care devices [8,9]. Pulmonary infections
due to P. aeruginosa may also arise hematogenously [10]. P. aeruginosa is also an important
cause of nosocomial tracheobronchitis [2]. (See "Epidemiology, pathogenesis, microbiology,
and diagnosis of hospital-acquired and ventilator-associated pneumonia in adults".)
Several risk factors for HAP due to P. aeruginosa have been identified. In one study, a higher
probability of P. aeruginosa pneumonia was associated with increased age, length of
mechanical ventilation, antibiotics at admission, transfer from a medical unit or ICU, and
admission in a ward with higher incidence of patients with P. aeruginosa infections [11]. A
lower probability of P. aeruginosa was associated with trauma and admission in a ward with
high patient turnover.
P. aeruginosa is a common cause of secondary bacterial pneumonia in individuals

hospitalized with COVID-19. (See "Epidemiology, microbiology, and pathogenesis of
Pseudomonas aeruginosa infection", section on 'Secondary infections in patients with
COVID-19'.)
Community-acquired pneumonia — In general, community-acquired P. aeruginosa

pneumonia is a rare occurrence. While its exact incidence is unknown, multi-national studies
show its prevalence to be around 4 percent [12]. Community-acquired P. aeruginosa
pneumonia is occasionally reported in otherwise healthy hosts [13]. In a recent review of the
literature on immunocompetent individuals who did develop community-acquired P.
aeruginosa, identified risk factors were [14]:
● Advanced age
● Smoking
● Alcohol use
● Exposure to contaminated liquids
Most patients have an identifiable risk factor for disease. Community-acquired P. aeruginosa
pneumonia occurs mainly in individuals who have [12,15-17]:
● A compromised immune system (eg, patients with HIV, solid organ or hematopoietic
cell transplant recipients, neutropenic hosts, and those on immunosuppressive or
immunomodulatory agents such as TNF-alfa inhibitors)
● Recent prior antibiotic use
● Structural lung abnormalities such as cystic fibrosis or bronchiectasis
● Repeated exacerbations of chronic obstructive pulmonary disease requiring frequent
glucocorticoid and/or antibiotic use
As an example, P. aeruginosa causes 5 to 7 percent of cases of community-acquired

pneumonia in patients with HIV [18,19]. In another retrospective study of over 10,000
patients hospitalized for pneumonia, P. aeruginosa was most highly associated with
bronchiectasis (adjusted odds ratio [aOR] = 6.13), lung abscess/empyema (aOR = 3.36), and
chronic obstructive pulmonary disease (COPD; aOR = 1.84), although the rate of P. aeruginosa
in patients with COPD but no other comorbidities was similar to the rate in the general
population [20]. Additional risk factors for community-acquired pneumonia due to P.
aeruginosa include cirrhosis [21], history of recent hospitalization [16], intubation [22], or
enteral tube feeding [23]. In one study, P. aeruginosa pneumonia was responsible for 39 out
of 559 cases of community-acquired pneumonia; previous hospital admission and
pulmonary comorbidity were predictive of the occurrence of this infection [16].
Person-to-person transmission of P. aeruginosa in the community is rare, but has been

reported in a few isolated instances. As an example, household spread was documented
when a daughter passed a P. aeruginosa strain to her mother, causing cavitary pneumonia
and lung abscess; the two isolates were confirmed to be identical using pulsed-field gel
electrophoresis [24].
Other rare risks for P. aeruginosa include environmental exposures. As an example, one
report described an isolated case of necrotizing P. aeruginosa pneumonia in an
immunocompetent patient that was attributed to contact with a contaminated hot tub filter.
This case highlights the importance of following the United States Centers for Disease
Control and Prevention (CDC) guidelines for hot tub maintenance to prevent Pseudomonas
overgrowth [25].
Equipment-related outbreaks — Outbreaks of P. aeruginosa infection linked to

contaminated health care equipment such as endoscopes have been occasionally reported
[26-28].
Bronchoscope contamination has been linked to defective design, bronchoscope damage,

and inadequate disinfection [29]. One outbreak related to defective bronchoscopes led to 32
cases of P. aeruginosa infections and three deaths prior to a voluntary recall of the
endoscopes by the manufacturer [27].
CLINICAL FEATURES
Signs and symptoms — Signs and symptoms of pneumonia caused by P. aeruginosa are
similar to those caused by other pyogenic bacteria and Legionella. No features can reliably
distinguish infection with P. aeruginosa from pneumonia caused by those other pathogens.
Acute P. aeruginosa pneumonia is usually characterized by cough productive of purulent
sputum, dyspnea, fever, chills, confusion, and severe systemic toxicity. Patients with
ventilator-associated P. aeruginosa pneumonia may also present with increased
tracheobronchial secretions and decreased ventilator performance that can develop
suddenly or gradually.
Although P. aeruginosa is typically associated with severe pneumonia, this is not a

distinguishing feature. In a study of 343 patients with hospital-acquired pneumonia, the
severity of illness was not associated with or predictive of microbial etiology [30].
The general clinical features of community- and hospital-acquired pneumonia (HAP) are
discussed elsewhere. (See "Clinical evaluation and diagnostic testing for community-acquired
pneumonia in adults", section on 'Clinical evaluation' and "Epidemiology, pathogenesis,
microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia in
adults", section on 'Diagnosis' and "Clinical presentation and diagnostic evaluation of
ventilator-associated pneumonia".)
Radiology — Radiographic findings are variable and no single finding is predictive or

characteristic of P. aeruginosa pneumonia. Diffuse bilateral infiltrates, with or without pleural
effusion, may be present. Many patients have multifocal airspace consolidation. Other
radiographic features include nodular infiltrates, tree-in-bud opacities, and necrosis [31].
Occasionally, areas of radiolucency suggestive of cavitary disease may be present. Classic
lobar consolidation is uncommon.
When P. aeruginosa pneumonia arises from hematogenous spread of the organism, early
radiographic findings may include pulmonary congestion and interstitial edema. However,
diffuse interstitial and alveolar infiltrates often develop 24 to 48 hours later in such patients.
Large hemorrhagic nodules with central necrosis or cavities may rarely occur later in the
course.
Radiographic findings in certain hosts may also have particular characteristics. As an

example, in a small study of 16 HIV-infected patients with P. aeruginosa pneumonia, of whom
the majority had low CD4 cell counts, 11 presented with or subsequently developed cavitary
infiltrates [32].
Pathology — Histopathologic changes in patients with pneumonia due to P. aeruginosa

typically include microabscesses with focal hemorrhage and necrosis of the alveolar septae
without evidence of bacterial invasion of vessel walls or vascular necrosis. Pathologic
changes in patients with pneumonia due to hematogenous spread usually include intra-
alveolar hemorrhage and necrosis around pulmonary vessels. Small (2 to 15 mm), firm,
yellow-brown necrotic nodules with dark red hemorrhagic parenchyma may also be present
along with liquefactive necrosis or bacterial invasion of the alveolar cell walls.
One autopsy study of eight infants with P. aeruginosa pneumonia revealed two distinct
histopathological patterns. Seven cases demonstrated evidence of a distinctive paucicellular
coagulative confluent bronchopneumonia with perivascular bacillary infiltration. These
changes occurred in immunocompromised patients with sepsis and rapid deterioration. The
eighth case, a patient with an unusually protracted clinical course, had pathologic changes
typical of bacterial pneumonia without evidence of perivascular organisms [33].
DIAGNOSIS
The diagnosis of P. aeruginosa pneumonia is made following the growth of P. aeruginosa on

culture of expectorated sputum, bronchoscopically obtained samples, or other respiratory
specimens in a patient with clinical and radiographic findings consistent with pneumonia.
The diagnostic evaluation for pneumonia is discussed in detail elsewhere. (See "Clinical
evaluation and diagnostic testing for community-acquired pneumonia in adults" and
"Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired and
ventilator-associated pneumonia in adults", section on 'Diagnosis' and "Clinical presentation
and diagnostic evaluation of ventilator-associated pneumonia", section on 'Diagnostic
evaluation'.)
In some cases, particularly in the settings of intubation or chronic bronchiectasis, which can
be associated with chronic growth of P. aeruginosa in the airways, the distinction between
respiratory infection and colonization with P. aeruginosa may be difficult to make. Changes in
clinical status such as new fever, new leukocytosis, new abnormality on chest imaging, and
worsened respiratory status are suggestive of pneumonia in patients chronically colonized
with P. aeruginosa. The use of quantitative cultures on sputum specimens from ventilated
patients may also be helpful in distinguishing between infection and colonization [34], but
these techniques are not widely available and their use in clinical practice is uncommon. (See
"Clinical presentation and diagnostic evaluation of ventilator-associated pneumonia", section

on 'Diagnostic evaluation'.)
MANAGEMENT
Empiric antimicrobial therapy — Until antimicrobial susceptibility results are available, we

initially treat known or suspected cases of P. aeruginosa pneumonia with a single
antimicrobial agent, unless the patient has sepsis or risk factors for a drug resistant
infection, in which case we use two antibiotics from different classes to which the isolate is
likely to be susceptible ( table 1).
Specifically, we agree with the guidelines from the Infectious Diseases Society of America
and the American Thoracic Society on the empiric management of community-acquired and
hospital-acquired pneumonia (HAP) that recommend the following antimicrobial
combinations for patients who have risk factors for both P. aeruginosa infection as well as
drug resistance [15,35]:
● An antipseudomonal beta-lactam PLUS an antipseudomonal quinolone

● An antipseudomonal beta-lactam PLUS an aminoglycoside
● An antipseudomonal quinolone PLUS an aminoglycoside
Antipseudomonal beta-lactams include piperacillin-tazobactam, ceftazidime, cefepime,

imipenem, and meropenem. Aztreonam may be substituted for one of these in the setting of
penicillin allergy. Antipseudomonal quinolones include ciprofloxacin and levofloxacin (750
mg dose).
Antimicrobial selection should also include consideration of local epidemiology and local
antimicrobial resistance patterns, particularly in patients at risk for multidrug-resistant P.
aeruginosa. In settings where multidrug resistance is common, novel expanded-spectrum
beta-lactam agents (such as ceftolozane-tazobactam) may be appropriate for empiric
therapy [36-44]. Additional details, including dosing, on antibiotic regimens for the treatment
of P. aeruginosa infections are found in the table ( table 1) and are elaborated on
elsewhere. (See "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections",
section on 'Intravenous antibiotics'.)
Risk factors for P. aeruginosa among patients presenting with hospital- or community-
acquired pneumonia are discussed elsewhere, as are risk factors for antimicrobial resistance.
(See 'Epidemiology' above and "Principles of antimicrobial therapy of Pseudomonas
aeruginosa infections", section on 'Antimicrobial resistance'.)
The evidence for combination versus monotherapy is also discussed separately. (See
"Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on 'Role
of combination antimicrobial therapy'.)
Directed antimicrobial therapy
Regimen choice — We suggest streamlining empiric combination therapy to a single active

antibiotic once susceptibility results are available ( table 1). We typically use a beta-lactam,
reserving carbapenems for treating polymicrobial infections or organisms resistant to other
agents. Advanced beta-lactams, such as ceftolozane-tazobactam, ceftazidime-avibactam, and
imipenem-cilastatin-relebactam, can be used as monotherapy, if active, for isolates of P.
aeruginosa that are resistant to the traditional antipseudomonal drugs [45]. In general,
aminoglycosides should not be used as monotherapy for pneumonia because they perform
poorly in an acidic environment.
Ceftolozane-tazobactam's efficacy in treating nosocomial pneumonia has been

demonstrated in the ASPECT-NP trial where it proved to be noninferior to meropenem in
terms of 28-day mortality [37]. In addition, the supplementary analysis to the ASPECT-NP trial
showed that ceftolozane-tazobactam prevented the emergence of resistance in P. aeruginosa
as opposed to the meropenem group, where 22.4 percent of the isolates became resistant
[46].Furthermore, its ability to enable shorter ICU stays and duration of mechanical
ventilation was demonstrated in separate studies [47]. Ceftolozane-tazobactam has also
proven superiority in terms of mortality with less risk of adverse effects when compared to
polymyxin or aminoglycoside-based regimens [48-50].
Real-world data have consistently shown ceftolozane-tazobactam's effectiveness and safety

[43,51-53].
In a multi-center, retrospective analysis of 206 patients with HAP/ventilator-associated

pneumonia (VAP) secondary to MDR or extensively drug-resistant (XDR) P. aeruginosa where
ceftolozane-tazobactam was compared to the best available therapy, treatment with
ceftolozane-tazobactam was independently associated with a 73.3 percent reduction in
clinical failure, compared to those who received best available therapy, along with a lower
rate of adverse events (10 versus 33 percent). Nephrotoxicity (85 percent) and Clostridioides
difficle infection (5 percent) were the most commonly side effects [52]. In another multicenter
study in which ceftolozane-tazobactam was used as outpatient therapy, where 18 percent of
infections were respiratory infections and 23 percent were secondary to P. aeruginosa, 95
percent of infections clinically resolved [53].
Ceftazidime-avibactam has also proven its efficacy in treating nosocomial pneumonia in the
REPROVE trial where it was found to be noninferior to meropenem [54].
Real-world data published so far for the treatment of HAP/VAP confirmed the high efficacy
and tolerability of this novel beta-lactam beta-lactamase inhibitor (BL-BLI) [55-58]. In the
largest cohort to date, ceftazidime-avibactam was assessed for severe pulmonary infections
due to carbapenem-resistant and difficult-to-treat P. aeruginosa; 63 percent achieved clinical

cure with bacterial eradication in 80 percent of the cases and an all-cause mortality of 19
percent by day 30 [57].
There are only a few studies that compared ceftolozane-tazobactam to ceftazidime-

avibactam. A recent multi-center retrospective cohort study compared both of these BL-BLIs
in treating P. aeruginosa infections and looked at overall in-hospital mortality, 30-day
mortality, and clinical cure, 28 percent of which were diagnosed with HAP and 21 percent
with VAP. The three outcomes were comparable in both groups. In addition, no difference
was found in other outcomes, including infection-related mortality, 30-day readmission, 30-
day recurrence, 90-day recurrence, microbiologic eradication, length of stay, or duration of
mechanical ventilation [59].
Imipenem-cilastatin-relebactam's safety and efficacy was evaluated in the RESTORE-IMI 1

study where it was compared to an imipenem/colistin combination in the treatment of
multiple infections, 35.5 percent of which were HAP/VAP, with the most common pathogen
being P. aeruginosa (77.4 percent) [60]. Its efficacy was re-affirmed in RESTORE IMI 2 where
imipenem-cilstatin-relebactam was compared to piperacillin-tazobactam in the treatment of
HAP/VAP [61].
Real-world data evaluating imipenem-cilastatin-relebactam is scarce [62,63]. However,

studies done so far have also demonstrated the high efficacy and safety of this BL-BLI. In a
multi-center observational study of 21 patients, where the most commonly evaluated
infection was respiratory tract infection (52 percent HAP/VAP) and the most common
pathogen was MDR P. aeruginosa (76 percent), 30-day mortality was 33 percent, which was
attributed to patients having comorbidities, whereas clinical cure was 62 percent. As for side
effects, only gastrointestinal symptoms and one case of encephalopathy were reported,
neither leading to drug discontinuation [62].
Cross-resistance remains an issue in regard to ceftolozane-tazobactam and ceftazidime-

avibactam because of high structural similarities. Accordingly, the IDSA recommended in
their recent guidance to always repeat antimicrobial susceptibility testing for newer BL-BLIs
when a previously infected patient with difficult-to-treat P. aeruginosa presents with new or
relapsed infection, with the consideration of the use of imipenem-cilastatin-relebactam or
cefiderocol if the patient was recently treated with ceftolozane-tazobactam or ceftazidime-
avibactam [64].
Cefiderocol, a new siderophore cephalosporin, has also demonstrated noninferiority in the

treatment of nosocomial pneumonia due to MDR GNB, 16 percent of which were secondary
to P. aeruginosa when compared to meropenem in terms of all-cause mortality at 14 days
[65].
Real-world data on cefiderocol use remains scarce [66-68]. In the largest recently performed
retrospective multi-center cohort study to date that included 142 patients, 51.1 percent of
who were diagnosed with pneumonia with 21.1 percent of all isolates being identified as P.
aeruginosa, 30-day mortality was shown to be 37 percent, with a higher absolute rate of
death in patients diagnosed with pneumonia (43 percent) [68].
Interestingly, in a study evaluating cross-resistance in P. aeruginosa isolates from patients

treated with the new BL-BLIs, cross-resistance between cefiderocol and ceftolozane-
tazobactam was evident, unlike with ceftazidime-avibactam and imipenem-relebactam [69].
Multiple antibiotics are currently in the pipeline, such as cefepime-taniborbactam, cefepime-

zidebactam, cefepime-enmetazobactam, sulbactam durlobactam, and murepavadin [70]. All
of these antibiotics, despite variable activity against carbapenemases, have demonstrated in
vitro activity against drug-resistant P. aeruginosa [71-75], with cefepime-taniborbactam amd
cefepime-zidebactam demonstrating in vivo bactericidal activity in murine lung infection
models [76,77]. These antibiotics are yet to be assessed for nosocomial pneumonia.
Murepavadin is a new class antibiotic that selectively inhibits the lipopolysaccharide (LPS)
protein D, a vital outer membrane protein involved in LPS biogenesis in Gram negative
bacteria. It has demonstrated specific antimicrobial activity against multiple Pseudomonas
spp including P. aeruginosa [78]. It was being evaluated in two clinical trials, PRISM-MDR and
PRISM-UDR; however, both trials were stopped due to significant nephrotoxicity with further
investigation of the molecule's safety required [79,80].
Although some experts continue a combination regimen as directed therapy in order to

minimize the emergence of antimicrobial resistance, there is little clinical evidence that
clearly demonstrates a benefit to directed combination therapy.
In a multicenter study of 183 patients with VAP due to P. aeruginosa, use of combination
therapy or monotherapy tailored to susceptibility results did not influence mortality, length
of stay, recurrent infection rate, or development of resistance [81]. In addition, a recent study
based on the patients included in the iDIAPASON trial, a multi-center randomized controlled
trial comparing 8- to 15-day antibiotic therapy for VAP secondary to P. aeruginosa, assessed
the outcomes of using mono- versus combination therapy and no difference was found [82].
Moreover, real-world data on the use of novel BL-BLIs and cefiderocol as part of combination
therapy have shown no difference in clinical outcomes [57,58,68]. In their latest update of
guidelines for the treatment of resistant organisms, the IDSA recommended against using
directed combination therapy in the treatment of difficult-to-treat P. aeruginosa, especially if
the organism is susceptible to one of the new BL-BLIs [64]. (See "Principles of antimicrobial
therapy of Pseudomonas aeruginosa infections", section on 'Role of combination
antimicrobial therapy'.)
Duration of therapy — The optimal duration of antimicrobial therapy for P. aeruginosa

pneumonia is uncertain. We individualize the duration based on the underlying
comorbidities and condition of the patient, the initial response to therapy, and the
susceptibility of the infecting isolate. Patients who have no significant comorbidities,
defervesce, and improve clinically within the first week of therapy, and those who have
infection with a susceptible P. aeruginosa isolate, can be treated with regimens as short as 7
to 10 days. However, longer treatment durations (eg, from 10 to 21 days) may be warranted
for patients with serious underlying conditions (eg, neutropenia), concurrent blood stream
infection, a poor or slow response to therapy, and/or a partially susceptible or multidrug-
resistant strain. If the isolate is susceptible to fluoroquinolones and there are no concerns
about gastrointestinal absorption of oral medications, the patient can transition to oral
ciprofloxacin or levofloxacin to complete the course.
Support for a relatively abbreviated course of antibiotics comes from several trials on
treatment of VAP, in which short (seven- to eight-day) courses of antibiotics resulted in
similar clinical cure and mortality rates and lower rates of recurrence with multidrug-
resistant organisms compared with longer (10- to 15-day) courses [83,84]. However, in some
studies, the recurrence rate for pneumonias caused by nonfermenting gram-negative bacilli
(such as P. aeruginosa) was higher with short courses. This finding was re-demonstrated in
the iDIAPASON study, a prospective multi-center randomized controlled open-label trial
where the percentage of recurrence of ventilator-associated P. aeruginosa during the ICU
stay was 9.2 percent in the 15-day group versus 17 percent in the 8-day group [85]. However,
the duration of therapy remains a matter of debate. In a recent editorial, panelists who
participated in the 2016 IDSA/ATS guidelines on ventilator-associated/HAP responded to a
viewpoint by Albin et al [86] arguing against the last IDSA/ATS guidelines recommending a
short course of VAP secondary to P. aerguinosa. Metersky et al argued that both major
studies that reported increased recurrence in short duration therapy were fully or partially
open-label; both studies did not account for the differential time-at-risk bias, leading to
patients in the short-course group being observed for recurrence at least 7 to 10 days more
than the opposing group. In addition, recurrence was not adequately assessed as both
studies showed no difference in length of stay, mechanical ventilator duration, or mortality
[87]. Thus, while a short course may be appropriate for some patients with P. aeruginosa
pneumonia, we favor a more conservative approach with a longer course of therapy in
patients who may have an especially high mortality because of comorbidities or according to
the clinical course.
The airway may remain colonized with P. aeruginosa even in the setting of clinical response.
Symptomatic improvement is a more important indicator than organism eradication for
decisions regarding timing of antibiotic discontinuation.
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Inhaled antibiotics for selected patients — We do not routinely use inhaled antibiotics for
the treatment of P. aeruginosa pneumonia.
In their latest guidance on the management of antibiotic-resistant organisms, the IDSA did
not recommend the use of nebulized antibiotics for the treatment of difficult-to-treat P.
aeruginosa [64]. This is mainly due to the lack of evidence suggesting improved outcomes or
higher survival rates even in subgroup analysis of resistant isolates, regardless of the
medication used (colistin, amikacin, fosfomycin) [88-90], in addition to concerns that these
medications may be causing damage to lung tissue. Similarly, the European Society of
Clinical Microbiology and Infectious Diseases (ESCMID) did not recommend inhaled antibiotic
therapy due to the lack of strong evidence of efficacy [91]. Nevertheless, inhaled antibiotics
can be used as an adjunct to intravenous therapy (IV) in cases of infection due to multidrug-
resistant strains.
Specifically, inhaled polymyxins have been used successfully in the management of

multidrug-resistant P. aeruginosa pneumonia failing to improve on IV therapy [92-95]. In a
retrospective study from Italy of patients with VAP due to gram-negative organisms sensitive
only to colistin, clinical cure rates were higher (69 versus 55 percent, p = 0.03) and duration
of post-VAP mechanical ventilation shorter (median 8 versus 12 days) among 104 patients (24
with P. aeruginosa) who received nebulized and IV colistin compared with 104 matched
patients (28 with P. aeruginosa) who received only IV colistin [95]. Nebulized colistin in
treatment of pneumonia due to multidrug-resistant Acinetobacter baumannii and P.
aeruginosa was evaluated in a retrospective study of 21 patients in Singapore [93]. Overall
clinical and microbiological response rates were 57 and 86 percent, respectively. Most
patients received 1 million units (approximately 80 mg) of colistin twice daily. There was no
significant change in renal function or observed neurotoxicity. (See "Polymyxins: An
overview".)
Colistin is approved by the FDA only for IV or intramuscular use; it is not approved as a liquid
to be inhaled via nebulizer. When the drug is mixed into a liquid form, the product can break
down into other chemicals that can damage lung tissue [96]. Instructions regarding
preparation of nebulized colistin are discussed separately. (See "Polymyxins: An overview".)
Other strategies for drug-resistant isolates — Drug-resistant P. aeruginosa infections

should be managed with the assistance of an expert in the treatment of multidrug-resistant
pathogens. Strategies for such infections include the use of inhaled antibiotics, alternative
intravenous agents, and certain combination regimens. These are discussed elsewhere. (See
'Inhaled antibiotics for selected patients' above and "Principles of antimicrobial therapy of
Pseudomonas aeruginosa infections", section on 'Management of multidrug-resistant
organisms'.)
Bacteriophage therapy has been described as potential treatment for extensively drug-
resistant P. aeruginosa infections in scattered case reports, including cases of lung infection
[97-99]. In one case report, it was used for seven days in addition to prolonged antibiotic
therapy in a woman with extensive necrotizing P. aeruginosa pneumonia, with subsequent
resolution of infection and microbiologic clearance; bacteriophage therapy was well
tolerated without adverse events detected during or after therapy [97]. Its use in the
literature has been mainly described as an adjunct to antibiotics with various formulations
used [100]. For instance, in their article describing three case reports of bacteriophage
therapy in lung transplant patients, Aslam et al mention a 67-year male who had two
episodes of MDR P. aeruginosa pneumonia post-transplant treated with IV and nebulized
phage therapy, used both therapeutically and as suppressive therapy [101]. In another report
by Chen et al, a 68-year-old man with broncho-pleural fistula-associated empyema and
pneumonia secondary to carbapenem-resistant P. aeruginosa was treated with both
nebulized and intrapleural phage therapy for 24 days in addition to IV antibiotics. The
pathogen was cleared, the patient clinically improved, and phage therapy was well tolerated
[102].
Other potential strategies under investigation for control of P. aeruginosa pneumonia include
immunotherapy and vaccination. These are discussed elsewhere. (See "Epidemiology,
microbiology, and pathogenesis of Pseudomonas aeruginosa infection", section on
'Investigational interventions based on pathogenesis'.)
OUTCOME AND PROGNOSIS
P. aeruginosa pneumonia is associated with high in-hospital mortality rates and prolonged
lengths of stay [4,29]. Injury to the alveolar epithelium allows the release of proinflammatory
mediators into the circulation that are primarily responsible for septic shock [103]. (See
"Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and
prognosis".)
P. aeruginosa pneumonia accompanied by P. aeruginosa bacteremia is associated with a

particularly poor prognosis, with death occurring three to four days after the first signs of
infection in the majority of cases.
Other factors significantly associated with a poor prognosis include [4,104-106]:
● Advanced age
● Serious underlying disease
● Septic shock
● Acute respiratory distress syndrome
● Previous surgery
● Comorbidities, such as diabetes mellitus

● Inadequate initial antibiotic therapy
● Use of broad-spectrum antibiotics in previous six months
● Multidrug-resistant organisms
As an example, in a study of 110 ICU patients with culture confirmed P. aeruginosa

pneumonia, inadequate initial antibiotic therapy, diabetes mellitus, disease severity (high
Simplified Acute Physiology Score [SAPS] II), and older age were independently associated
with ICU mortality [106]. Among survivors, inappropriate initial antibiotic therapy and
infection with multidrug-resistant P. aeruginosa infection were each associated with longer
post-pneumonia mechanical ventilation time.
In one retrospective study of patients with hospital-acquired P. aeruginosa pneumonia,

receipt of inadequate initial antibiotic therapy was associated with a substantially higher
mortality rate compared with adequate therapy (64 versus 25 percent) [106].
PSEUDOMONAS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Isolation of P. aeruginosa from sputum samples of adult patients with COPD is associated
with advanced pulmonary disease [107].
● In one cross-sectional study, patients with a predicted FEV1 of less than 50 percent were
more likely to have H. influenzae or P. aeruginosa isolated from sputum during
exacerbations than patients with less severe impairment of pulmonary function [108].
● Another study demonstrated that in patients who had FEV1 less than 35 percent the
predicted value, Enterobacterales and Pseudomonas species were the predominant
isolated bacteria from sputum [109].
● In a separate study, the presence of enteric gram-negative bacilli and P. aeruginosa in

the sputum of patients during exacerbations could be predicted by severe airflow
obstruction [110].
● Furthermore, exacerbations in the presence of P. aeruginosa in the sputum are linked to

respiratory failure and the need for mechanical ventilation. These interpretations may
suggest that P. aeruginosa is a more frequent cause of infection as COPD progresses.
There exists a subset of patients with COPD who become chronically colonized with P.
aeruginosa, but whether such patients benefit from antimicrobial therapy is still unclear.
SUMMARY AND RECOMMENDATIONS
● Hospital-acquired pneumonia – P. aeruginosa is a common cause of gram-negative

hospital-acquired pneumonia, which can occur via aspiration of endogenous oral flora,
via aspiration of organisms from contaminated ventilator tubing or other health care
devices, or through hematogenous spread. (See 'Hospital-acquired pneumonia' above.)
● Community-acquired pneumonia – Community-acquired P. aeruginosa pneumonia

occurs mainly in immunocompromised patients (eg, HIV-infected patients, solid organ
or stem cell transplant recipients, or neutropenic hosts), those with recent prior
antibiotic use, and those with structural lung abnormalities such as cystic fibrosis,
bronchiectasis, or repeated exacerbations of chronic obstructive pulmonary disease
requiring frequent glucocorticoid and/or antibiotic use. (See 'Community-acquired
pneumonia' above.)
● Clinical manifestations – P. aeruginosa pneumonia is usually characterized by cough

productive of purulent sputum, dyspnea, fever, chills, confusion, and severe systemic
toxicity. None of these manifestations firmly distinguish this infection from pneumonia
caused by other pyogenic organisms or Legionella. Radiographic findings are variable
and no single finding is predictive or characteristic of P. aeruginosa pneumonia. (See
'Clinical features' above.)
● Diagnosis – The diagnosis of P. aeruginosa pneumonia is made following the growth of

P. aeruginosa on culture of expectorated sputum, bronchoscopically-obtained samples,
or other respiratory specimens in a patient with clinical and radiographic findings
consistent with pneumonia. (See 'Diagnosis' above and "Epidemiology, pathogenesis,
microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia
in adults".)
● Empiric antibiotic selection – Until antimicrobial susceptibility results are available,

suspected cases of P. aeruginosa pneumonia can be empirically treated with a single
antimicrobial agent, unless the patient has sepsis or risk factors for a drug resistant
infection, in which case we use two antibiotics from different classes to which the
isolate is likely to be susceptible ( table 1). The rationale for combination versus
monotherapy is discussed elsewhere. (See 'Empiric antimicrobial therapy' above and
"Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on
'Role of combination antimicrobial therapy'.)
● Targeted antibiotics – Once susceptibility testing results are available, we suggest use
of a single active antibiotic for directed therapy of susceptible infections instead of
combination therapy (Grade 2B). Patients who have no significant comorbidities,
defervesce and improve clinically within the first week of therapy, and those who have
infection with a susceptible P. aeruginosa isolate can be treated with regimens as short
as 7 to 10 days. Longer treatment durations (eg, from 10 to 21 days) may be warranted

for other patients. (See 'Directed antimicrobial therapy' above.)
● Management of multidrug resistance – Multidrug-resistant P. aeruginosa infections

should be managed with the assistance of an expert in the treatment of such infections.
Alternative agents such as colistin may be necessary. Other possible strategies for
resistant infections include the use of inhaled antibiotics, combination regimens, and
alternative dosing strategies. (See 'Inhaled antibiotics for selected patients' above and
"Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on
'Management of multidrug-resistant organisms'.)
● Prognosis – P. aeruginosa pneumonia is associated with high in-hospital mortality rates

and prolonged lengths of stay. (See 'Outcome and prognosis' above.)
ACKNOWLEDGMENT
The UpToDate editorial staff acknowledges Daniel Sexton, MD, who contributed to earlier
versions of this topic review.
Use of UpToDate is subject to the Terms of Use.
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Topic 3133 Version 27.0
GRAPHICS
Antibiotics used for the treatment of Pseudomonas aeruginosa infections in

adults
Class Agent Dose
Penicillin-beta-lactamase Piperacillin-tazobactam 4.5 g IV every 6 hours

combinations*
Ticarcillin-clavulanate (not 3.1 g IV every 4 hours
available in the United States or
Canada)
Cephalosporins Ceftazidime 2 g IV every 8 hours
Cefepime 2 g IV every 8 or 12 hours ¶
Cefoperazone 2 g IV every 12 hours
Cefiderocol Δ 2 g IV every 8 hours
Monobactams Aztreonam 2 g IV every 8 hours
Fluoroquinolones ◊ Ciprofloxacin 400 mg IV every 8 to 12 hours o

750 mg orally every 12 hours
Levofloxacin 750 mg IV or orally once daily
Carbapenems § Meropenem 1 g IV every 8 hours
Doripenem 500 mg IV every 8 hours
Imipenem 500 mg IV every 6 hours ¥
Advanced beta-lactamase Ceftazidime-avibactam 2.5 g IV every 8 hours

inhibitor combinations Δ
Ceftolozane-tazobactam 1.5 to 3 g IV every 8 hours ‡
Imipenem-cilastatin-relebactam 1.25 g IV every 6 hours
Aminoglycosides † Tobramycin Dosing of aminoglycosides is

discussed in detail in a
Gentamicin
dedicated topic
Amikacin
Plazomicin
Polymyxins** Colistin Dosing of polymyxins is

discussed in detail in a
Polymyxin B dedicated topic
Doses refer to intravenous administration. Doses listed are for patients with normal renal function;
dose adjustments may be warranted for renal impairment.
IV: intravenous; MIC: minimum inhibitory concentration.
* Ticarcillin (3 g every 4 hours) and piperacillin (4 g every 4 hours) each have antipseudomonal activity
but are not available in the United States as single agents without the beta-lactamase inhibitor.
¶ We aim to use the higher dose, particularly for severe infections or neutropenic patients, but dosing
should take into account the condition treated, the MIC of the isolate, the potential for toxicity, and
other patient specific factors.
Δ The novel cephalosporin cefiderocol and combination agents that include a cephalosporin or
carbapenem plus a beta-lactamase inhibitor are generally reserved for infections resistant to other
agents. The addition of vaborbactam to meropenem does not enhance the clinical activity of
meropenem against carbapenem-resistant P. aeruginosa.
◊ Fluoroquinolones are the only class of antibiotics with antipseudomonal activity that have an oral
formulation.
§ Carbapenems given as a single therapy have the propensity to induce resistance during treatment.
¥ Among the carbapenems, we favor meropenem or doripenem over imipenem, which has a higher
propensity to induce resistance during treatment. For severe infection (eg, septic shock), imipenem
can be given up to a dose of 1 g every 8 hours.
‡ Pulmonary infections are treated with the 3 g every 8 hour dose.
† Aminoglycosides are generally used in combination with a beta-lactam and should NOT be used as a
single agent for infections other than those of the lower urinary tract. When using an aminoglycoside
as part of therapy for an infection with a high risk of P. aeruginosa, we favor tobramycin over
gentamicin as it has greater intrinsic antipseudomonal activity; however, it may not be widely
available.
** Polymyxins are generally reserved for the treatment of serious infections caused by P. aeruginosa
isolates resistant to other agents. In such cases, they are often administered in combination with
other antimicrobial agents and with a loading dose preceding the standing dose. Refer to other
UpToDate content for more details on polymyxin dosing.
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21/2/24, 20:12 Pseudomonas aeruginosa pneumonia - UpToDate

Official reprint from UpToDate®

Pseudomonas aeruginosa pneumonia

Literature review current through: Jan 2024.

The clinical manifestations, diagnosis, and treatment of P. aeruginosa pneumonia will be

The general principles of antimicrobial treatment of infections caused by P. aeruginosa,

● (See "Epidemiology, microbiology, and pathogenesis of Pseudomonas aeruginosa

Hospital-acquired pneumonia — P. aeruginosa is a common cause of gram-negative

P. aeruginosa is a common cause of secondary bacterial pneumonia in individuals

Community-acquired pneumonia — In general, community-acquired P. aeruginosa

As an example, P. aeruginosa causes 5 to 7 percent of cases of community-acquired

Person-to-person transmission of P. aeruginosa in the community is rare, but has been

Equipment-related outbreaks — Outbreaks of P. aeruginosa infection linked to

Bronchoscope contamination has been linked to defective design, bronchoscope damage,

Although P. aeruginosa is typically associated with severe pneumonia, this is not a

Radiology — Radiographic findings are variable and no single finding is predictive or

Radiographic findings in certain hosts may also have particular characteristics. As an

Pathology — Histopathologic changes in patients with pneumonia due to P. aeruginosa

The diagnosis of P. aeruginosa pneumonia is made following the growth of P. aeruginosa on

"Clinical presentation and diagnostic evaluation of ventilator-associated pneumonia", section

Empiric antimicrobial therapy — Until antimicrobial susceptibility results are available, we

● An antipseudomonal beta-lactam PLUS an antipseudomonal quinolone

Antipseudomonal beta-lactams include piperacillin-tazobactam, ceftazidime, cefepime,

of combination antimicrobial therapy'.)

Directed antimicrobial therapy

Regimen choice — We suggest streamlining empiric combination therapy to a single active

Ceftolozane-tazobactam's efficacy in treating nosocomial pneumonia has been

Real-world data have consistently shown ceftolozane-tazobactam's effectiveness and safety

In a multi-center, retrospective analysis of 206 patients with HAP/ventilator-associated

due to carbapenem-resistant and difficult-to-treat P. aeruginosa; 63 percent achieved clinical

There are only a few studies that compared ceftolozane-tazobactam to ceftazidime-

Imipenem-cilastatin-relebactam's safety and efficacy was evaluated in the RESTORE-IMI 1

Real-world data evaluating imipenem-cilastatin-relebactam is scarce [62,63]. However,

Cross-resistance remains an issue in regard to ceftolozane-tazobactam and ceftazidime-

Cefiderocol, a new siderophore cephalosporin, has also demonstrated noninferiority in the

Interestingly, in a study evaluating cross-resistance in P. aeruginosa isolates from patients

Multiple antibiotics are currently in the pipeline, such as cefepime-taniborbactam, cefepime-

Although some experts continue a combination regimen as directed therapy in order to

Duration of therapy — The optimal duration of antimicrobial therapy for P. aeruginosa

Specifically, inhaled polymyxins have been used successfully in the management of

Other strategies for drug-resistant isolates — Drug-resistant P. aeruginosa infections

OUTCOME AND PROGNOSIS

P. aeruginosa pneumonia accompanied by P. aeruginosa bacteremia is associated with a

Other factors significantly associated with a poor prognosis include [4,104-106]:

● Comorbidities, such as diabetes mellitus

As an example, in a study of 110 ICU patients with culture confirmed P. aeruginosa

In one retrospective study of patients with hospital-acquired P. aeruginosa pneumonia,

PSEUDOMONAS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

● In a separate study, the presence of enteric gram-negative bacilli and P. aeruginosa in

● Furthermore, exacerbations in the presence of P. aeruginosa in the sputum are linked to

SUMMARY AND RECOMMENDATIONS

● Hospital-acquired pneumonia – P. aeruginosa is a common cause of gram-negative

● Community-acquired pneumonia – Community-acquired P. aeruginosa pneumonia

● Clinical manifestations – P. aeruginosa pneumonia is usually characterized by cough

● Diagnosis – The diagnosis of P. aeruginosa pneumonia is made following the growth of

● Empiric antibiotic selection – Until antimicrobial susceptibility results are available,

as 7 to 10 days. Longer treatment durations (eg, from 10 to 21 days) may be warranted