# 53 - 170 Infections Due to Pseudomonas, Burkholderia, and Stenotrophomonas Species

### 170 Infections Due to Pseudomonas, Burkholderia, and Stenotrophomonas Species

Kartikeya Cherabuddi, Reuben Ramphal

Infections Due to 

Pseudomonas, Burkholderia, 

and Stenotrophomonas Species
The pseudomonads are a heterogeneous group of gram-negative 
bacteria that have in common an inability to ferment lactose. Formerly 
classified in the genus Pseudomonas, the members of this group have been 
assigned to three medically important genera—Pseudomonas, Burkhold­
eria, and Stenotrophomonas—whose biologic behaviors encompass both 
similarities and marked differences and whose genetic repertoires differ 
in many respects. The pathogenicity of most pseudomonads is based on 
opportunism; the exceptions are Burkholderia pseudomallei and 
Burkholderia mallei, which are primary pathogens.
The genus Pseudomonas now contains >140 species. Pseudomonas 
aeruginosa, the major pathogen of the group, is a significant cause of 
infections in hospitalized patients and in patients with cystic fibrosis 
(CF; Chap. 302). Cytotoxic chemotherapy, mechanical ventilation, 
chronic lung diseases, and broad-spectrum antibiotic therapy set up 
conditions that predispose to colonization and infection of increasing 
numbers of hospitalized patients by this pathogen. Other significant 
members of the genus—Pseudomonas putida, Pseudomonas fluorescens, 
Pseudomonas oryzihabitans, and Pseudomonas stutzeri—infect humans 
infrequently and are generally opportunists that are always present in 
the environment.
The genus Burkholderia comprises >20 species, of which Burk­
holderia cepacia is most frequently encountered in Western countries. 
Similar to P. aeruginosa, B. cepacia (now referred to as the B. cepacia 
complex species) is both an opportunistic nosocomial pathogen and 
a cause of infection in CF. The other medically important members 
of this genus are B. pseudomallei and B. mallei, the etiologic agents of 
melioidosis and glanders, respectively.
The genus Stenotrophomonas contains one species of medical sig­
nificance, Stenotrophomonas maltophilia. This organism is strictly an 
opportunist that “overgrows” in the setting of broad-spectrum antibi­
otic use.
PSEUDOMONAS AERUGINOSA
■
■EPIDEMIOLOGY
P. aeruginosa is found in most moist environments. Soil, plants, veg­
etables, tap water, and countertops are all potential reservoirs for this 
microbe, as it has simple nutritional needs. Given the ubiquity 
of P. aeruginosa, it is clear that simple contact with the organism is 
not sufficient for colonization or infection. Clinical and experimental 
observations suggest that infection by P. aeruginosa occurs concomi­
tantly with compromised host defenses, mucosal trauma, physiologic 
derangement, and antibiotic-mediated suppression of normal flora. 
Thus, it comes as no surprise that the majority of P. aeruginosa infec­
tions occur in intensive care units (ICUs), where these factors fre­
quently converge. Although the organism is initially acquired from 
environmental sources, patient-to-patient spread occurs in CF clinics 
and may occur in closed hospital units.
In the past, patients with burns appeared to be unusually suscep­
tible to P. aeruginosa. For example, in 1959–1963, Pseudomonas burnwound sepsis was the principal cause of death in 60% of patients with 
burns dying at the U.S. Army Institute of Surgical Research. For reasons 
that are unclear, P. aeruginosa infection in burns is no longer the major 
problem that it was during the 1950s and 1960s. Similarly, in the 1960s, 
P. aeruginosa appeared as a common pathogen in patients receiving 
cytotoxic chemotherapy at many institutions in the United States, but 
it has subsequently diminished in importance. Despite this subsidence, 

P. aeruginosa remains one of the most feared pathogens in this population 
because of its high attributable mortality.

In some parts of Asia and Latin America, P. aeruginosa continues to 
be the most common cause of gram-negative bacteremia in neutrope­
nic patients.

In contrast to the trends for patients with burns or neutropenia 
in the United States, the incidence of P. aeruginosa infections among 
patients with CF has not changed. P. aeruginosa remains the most com­
mon contributing factor to respiratory failure in CF and is responsible 
for the majority of deaths among CF patients.
■
■LABORATORY FEATURES
P. aeruginosa is a nonfastidious, motile, gram-negative rod that grows 
on most common laboratory media, including blood and MacConkey 
agars. It is easily identified in the laboratory on primary-isolation agar 
plates by pigment production that confers a yellow to dark green or 
even bluish appearance. Colonies have a shiny “gun-metal” appearance 
and a characteristic fruity odor. Two of the identifying biochemical 
characteristics of P. aeruginosa are an inability to ferment lactose on 
MacConkey agar and a positive reaction in the oxidase test. Most 
strains are identified on the basis of these readily detectable labora­
tory features even before extensive biochemical testing is done. Some 
isolates from CF patients are easily identified by their mucoid appear­
ance, which is due to the production of large amounts of the mucoid 
exopolysaccharide or alginate. Recently, there has been increasing use 
of molecular testing with multiplex polymerase chain reaction (PCR) 
platforms, which rapidly identify P. aeruginosa in respiratory and blood 
samples much earlier than the classical methods.
■
■PATHOGENESIS
Unraveling the mechanisms that underlie disease caused by P. aeruginosa 
has proved challenging. Of the common gram-negative bacteria, no 
other species produces such a large number of putative virulence fac­
tors (Table 170-1). Yet P. aeruginosa rarely initiates an infectious pro­
cess in the absence of host injury or compromise, and few of its putative 
virulence factors have been shown definitively to be involved in disease 
in humans. Despite its metabolic versatility and possession of multiple 
colonizing factors, P. aeruginosa exhibits no competitive advantage 
over enteric bacteria in the human gut; it is not a normal inhabitant of 
the healthy human gastrointestinal tract, despite the host’s continuous 
environmental exposure to the organism.
CHAPTER 170
Infections Due to Pseudomonas, Burkholderia, and Stenotrophomonas Species
Virulence Attributes Involved in Acute P. aeruginosa Infec­
tions 
• 
MOTILITY AND COLONIZATION  A general tenet of bac­
terial pathogenesis is that most bacteria must adhere to surfaces or 
colonize a host niche in order to initiate disease. Most gram-negative 
bacteria examined thus far possess adherence factors called adhesins. 
P. aeruginosa is no exception. Among its many adhesins are its pili, 
which demonstrate adhesive properties for a variety of cells and adhere 
best to injured cell surfaces. In the organism’s flagellum, the flagel­
lin molecule binds to cells, and the flagellar cap attaches to mucins 
through the recognition of glycan chains. Other P. aeruginosa adhesins 
TABLE 170-1  Main Putative Virulence Factors of Pseudomonas 
aeruginosa
SUBSTANCE/
ORGANELLE
FUNCTION
VIRULENCE IN ANIMAL 
DISEASE
Pili
Adhesion to cells
?
Flagella
Adhesion, motility, 
inflammation
Yes
Lipopolysaccharide
Antiphagocytic activity, 
inflammation
Yes
Type III secretion system
Toxic activity (ExoU, 
ExoS)
Yes
Type II secretion system
Toxic activity
Yes
Proteases
Proteolytic activity
?
Phospholipases
Cytotoxicity
?
Exotoxin A
Cytotoxicity
?
Pyocyanin
Cytotoxicity
Yes

include the outer core of the lipopolysaccharide (LPS) molecule, which 
binds to the cystic fibrosis transmembrane conductance regulator 
(CFTR) and aids in internalization of the organism, and the alginate 
coat of mucoid strains, which enhances adhesion to cells and mucins. 
In addition, membrane proteins and lectins have been proposed as 
colonization factors. The deletion of any given adhesin by itself is not 
sufficient to abrogate the ability of P. aeruginosa to colonize surfaces 
probably because of the redundancy of adhesins. Motility is important 
in host invasion via mucosal surfaces or burned skin in animal models 
of infection; however, nonmotile strains are not uniformly avirulent. It 
has been well demonstrated that nonmotile strains of P. aeruginosa are 
poorly phagocytosed in vitro, possibly leading to enhancement of the 
virulence of this organism in vivo.

EVASION OF HOST DEFENSES  The transition from bacterial coloniza­
tion to disease requires the evasion of host defenses followed by inva­
sion by the microorganism. P. aeruginosa appears to be well equipped 
for evasion. Attached bacteria inject four known toxins (ExoS or ExoU, 
ExoT, and ExoY) via a type III secretion system that allows the bacteria 
to evade phagocytic cells either by direct cytotoxicity or by inhibi­
tion of phagocytosis. Clinical studies suggest that the mortality rate is 
higher among patients infected by strains that secrete the ExoU toxin. 
Another secretion system—the type II system—secretes toxins that 
can kill animals, and some of its secreted toxins, such as exotoxin A, 
have the potential to kill phagocytic cells. Multiple proteases secreted 
by this system may degrade host effector molecules, such as cytokines 
and chemokines, that are released in response to infection and appear 
to play a role in corneal infections in mice.
TISSUE INJURY  Among gram-negative bacteria, P. aeruginosa prob­
ably produces the largest number of substances that are toxic to cells 
and thus have the potential to injure tissues. The toxins secreted by 
the organism’s type III secretion system are capable of injuring tissue. 
However, their delivery requires the adherence of the organism to cells. 
Thus, the effects of these toxins are likely to be local or to depend on 
the presence of large numbers of bacteria at the site of an infection 
or in the bloodstream. On the other hand, diffusible toxins, secreted 
by the organism’s type II secretion system, can act freely wherever 
they come into contact with cells. Possible effectors of this system 
include exotoxin A, at least four different proteases, and at least two 
phospholipases. In addition to these secreted toxins, rhamnolipids, 
pyocyanins—the pigments that confer the characteristic color and 
odor of P. aeruginosa colonies—and hydrocyanic acid, are produced by 
P. aeruginosa and are all capable of causing host tissue injury and even 
neutrophil death.
PART 5
Infectious Diseases
INFLAMMATORY COMPONENTS  The inflammatory responses to the 
lipid A component of Pseudomonas LPS and to its flagellin, mediated 
through the Toll-like receptor (TLR) system (principally TLR4 and 
TLR5, respectively), are thought to represent important factors in dis­
ease causation. Although these inflammatory responses are required 
for successful defense against P. aeruginosa (i.e., in their absence, ani­
mals are defenseless against P. aeruginosa infection), florid responses 
are likely to result in severe disease. Thus, when the sepsis syndrome 
and septic shock develop in P. aeruginosa infection, they are probably 
the result of the host response to one or both of these substances, but 
injury to the lung by Pseudomonas toxins may also result in sepsis 
syndromes, possibly by causing cell death and the release of cellular 
components (e.g., heat-shock proteins) that may activate the TLR or 
another proinflammatory system. Thus, the virulence of this bacterium 
in acute infections is likely to be multifactorial with a great redundancy 
of effector molecules being produced.
Chronic P. aeruginosa Infections 
Chronic infection due to P. 
aeruginosa occurs mainly in the lungs in the setting of structural 
pulmonary diseases. The classic example is CF; others include bron­
chiectasis and chronic relapsing panbronchiolitis, a disease seen in 
Japan and some Pacific Islands. A hallmark of these illnesses is severely 
defective mucociliary clearance leading to mucus stasis and mucus 
accumulation in the lungs. There is probably a common factor that 
selects for P. aeruginosa colonization in these lung diseases—perhaps 

the adhesiveness of P. aeruginosa for mucus, a phenomenon that is 
not noted for most other common gram-negative bacteria, and/or the 
ability of P. aeruginosa to evade host defenses in mucus. Furthermore, 

P. aeruginosa undergoes evolutionary adaptations and diversification in 
ways that allow its prolonged survival in the lung without an early fatal 
outcome for the host. The strains found in CF patients exhibit minimal 
production of virulence factors. Many strains lose the ability to pro­
duce pili and flagella, and most become complement-sensitive because 
of the loss of the O side chain of their LPS molecules. In addition, most 
strains found in CF patients overproduce a mucoid exopolysaccharide. 
These changes probably dampen the host response, allowing the organ­
ism to survive in CF mucus. P. aeruginosa is also believed to lose its 
ability to secrete many of its injectable toxins during growth in mucus. 
Although the alginate coat is thought to play a role in the organism’s 
survival, alginate is not essential as nonmucoid strains may predomi­
nate for long periods. In short, virulence in chronic infections may be 
mediated by the chronic but attenuated host inflammatory response, 
which injures the lungs over decades.
■
■CLINICAL MANIFESTATIONS
P. aeruginosa causes infections at almost all sites in the body but shows 
a rather marked predilection for the lungs. The infections encountered 
most commonly in hospitalized patients are described below.
Bacteremia 
Crude mortality rates exceeding 50% have been 
reported among patients with P. aeruginosa bacteremia. Consequently, 
this clinical entity has been much feared, and its management has 
been attempted with the use of multiple antibiotics. Recent publica­
tions report attributable mortality rates of 28–44%, with the precise 
figure depending on the adequacy and timing of treatment and the 
seriousness of the underlying disease. In the past, the patient with P. 
aeruginosa bacteremia classically was neutropenic or had a burn injury. 
Today, however, a minority of such patients have bacteremic P. aeruginosa 
infections. Rather, P. aeruginosa bacteremia is seen most often in 
patients in ICUs, with the lungs, the urinary tract, central venous lines, 
or wounds being the most important portals for systemic invasion.
The clinical presentation of P. aeruginosa bacteremia rarely differs 
from that of sepsis in general (Chap. 315). Patients are usually febrile, 
but those who are most severely ill may be in shock or even hypother­
mic. The only point differentiating this entity from gram-negative sep­
sis due to other bacteria may be the distinctive skin lesions (ecthyma 
gangrenosum) of Pseudomonas infection, which occur almost exclu­
sively in markedly neutropenic patients and patients with AIDS. 
These small or large, painful, reddish, maculopapular lesions have a 
geographic margin; they are initially pink, then darken to purple, and 
finally become black and necrotic (Fig. 170-1). Histopathologic studies 
indicate that the lesions are due to vascular invasion and are teeming 
with bacteria. Although similar lesions may occur in aspergillosis, 
mucormycosis, and occasionally Staphylococcus aureus bacteremia, 
their presence in a neutropenic patient generally suggests P. aeruginosa 
bacteremia as the most likely cause.
TREATMENT
P. aeruginosa Bacteremia
(Table 170-2) Antimicrobial treatment of P. aeruginosa bacte­
remia has been controversial. Combination therapy with an 
FIGURE 170-1  Ecthyma gangrenosum in a neutropenic patient 3 days after onset.

TABLE 170-2  Antibiotic Treatment of Infections Due to Pseudomonas aeruginosa and Related Species
INFECTION
ANTIBIOTICS AND DOSAGES
OTHER CONSIDERATIONS
Bacteremia
  Nonneutropenic host
Ceftazidime (2 g q8h IV) or cefepime (2 g q8h IV) or 
piperacillin/tazobactam (4.5 g q6h IV) or imipenem (500 mg 
q6h IV) or meropenem (1–2 g q8h IV) or doripenem (500 mg 
q8h IV)
Optional:
Amikacin (7.5 mg/kg q12h or 15 mg/kg q24h IV)
  Neutropenic host
Cefepime (2 g q8h IV) or any of the other agents above 
(except doripenem) in the above dosages
Endocarditis
Antibiotic regimens as for bacteremia for 6–8 weeks
Resistance during therapy is common. Surgery is required for 
relapse.
Pneumonia
Drugs and dosages as for bacteremia, except that the 
available carbapenems should not be the sole primary drugs 
because of high rates of resistance during therapy.
Bone infection, malignant otitis 
externa
Cefepime or ceftazidime at the same dosages as for 
bacteremia; aminoglycosides not a necessary component of 
therapy; ciprofloxacin (500–750 mg q12h PO) may be used
Central nervous system infection
Ceftazidime or cefepime (2 g q8h IV) or meropenem 

(2 g q8h IV)
Eye infection
  Keratitis/ulcer
Topical therapy with tobramycin/ciprofloxacin/levofloxacin 
eyedrops
  Endophthalmitis
Ceftazidime or cefepime as for central nervous system 
infection
plus
Topical therapy
Urinary tract infection (UTI)
Ciprofloxacin (500 mg q12h PO) or levofloxacin (750 mg q24h) 
or any aminoglycoside (total daily dose given once daily). 
Cefepime or ceftazidime (1g q8h) or piperacillin/tazobactam 
(3.375 g q6h)
Multidrug- and extreme drugresistant P. aeruginosa infection
Ceftazidime/avibactam (2.5 g q8h, infused over 2 h) or 
ceftolozane/tazobactam (1.5–3 g q8h) or imipenem/
relebactam (500 mg q6h) or cefiderocol (2 g q8h) or colistin 
(100 mg q12h IV for the shortest possible period to obtain a 
clinical response)
Burkholderia cepacia complex 
infection
Meropenem (2 g q8h IV) or TMP-SMX (1600/320 mg q12h IV) 
for 14 days
Melioidosis (B. pseudomallei), 
glanders (B. mallei)
Ceftazidime (2 g q6h) or meropenem (1 g q8h) or imipenem 
(500 mg q6h) for 2 weeks
followed by
TMP-SMX (1600/320 mg q12h PO) for 3 months
Stenotrophomonas maltophilia 
infection
TMP-SMX (1600/320 mg q12h IV) plus either
levofloxacin (750 mg q24h) or minocycline (100-200 mg q12h) 
or ticarcillin/clavulanate (3.1 g q4h IV) for 7 to 14 days
Abbreviations: MIC, minimum inhibitory concentration; TMP-SMX, trimethoprim-sulfamethoxazole.
antipseudomonal β-lactam and an aminoglycoside became the 
standard of care because of the dismal outcome of single-drug ther­
apy, mainly with aminoglycosides and polymixins, prior to 1971—
first for P. aeruginosa bacteremia in febrile neutropenic patients and 
then extrapolated to all P. aeruginosa bacteremic infections in both 
neutropenic and nonneutropenic patients.
Following the introduction of new antipseudomonal drugs, a 
number of studies have revisited the choice between combina­
tion treatment and monotherapy for Pseudomonas bacteremia. 
Although some clinicians still favor combination therapy, most 
recent observational studies indicate that a single modern antip­
seudomonal β-lactam agent to which the isolate is sensitive is as 
efficacious as a combination. Even in patients at greatest risk of 
early death from P. aeruginosa bacteremia (i.e., those with fever and 
neutropenia), empirical antipseudomonal monotherapy is deemed 
to be as efficacious as empirical combination therapy by the practice 
guidelines of the Infectious Diseases Society of America (IDSA). 

Add an aminoglycoside empirically for patients in shock and in 
regions or hospitals where rates of resistance to the primary 
β-lactam agents are high. Tobramycin may be used instead of 
amikacin (susceptibility permitting). A duration of 6–10 days of 
therapy can be used for uncomplicated bacteremia.
Febrile neutropenic patients should be treated until no longer 
neutropenic.
Add aminoglycoside or ciprofloxacin, as for bacteremia, until 
sensitivities available. The duration of therapy is 7 days.
Duration of therapy varies with the drug used and type of infection 
(e.g., 6 weeks for a β-lactam agent; except in puncture-wound 
osteomyelitis, for which the duration should be 2–4 weeks; oral 
therapy can be used).
Abscesses or other closed-space infections may require drainage. 
The duration of therapy is ≥2 weeks.
Use maximal strengths available or compounded by pharmacy. 
Therapy should be administered for 2 weeks or until the resolution 
of eye lesions, whichever is shorter.
 
CHAPTER 170
Uncomplicated cystitis may be treated for 3 days with oral agents. 
Relapse may occur if an obstruction or a foreign body is present. 
The duration of therapy for complicated cystitis and uncomplicated 
pyelonephritis is 5–7 days.
Infections Due to Pseudomonas, Burkholderia, and Stenotrophomonas Species
Use 3-g dose of ceftolozane/tazobactam for pneumonia. 
Meropenem-vaborbactam offers minimal benefit in carbapenem 
resistant strains. Alternatives to colistin are preferred, if available. 
Colistin dosing requires renal adjustment and expertise in its use. 
Inhaled colistin may be added for pneumonia (100 mg q12h).
Resistance to both agents is increasing. Do not use them in 
combination because of possible antagonism.
 
Broad-spectrum antibiotic therapy leads to respiratory tract 
colonization and often warrants no treatment. Ceftazidimeavibactam plus aztreonam, cefiderocol, or tigecycline are 
alternatives for XDR strains. Combination therapy should be used 
for bacteremia, especially in immunosuppressed patients.
One firm conclusion is that monotherapy with an aminoglycoside 
is not optimal.
There are, of course, institutions and countries where rates of 
susceptibility of P. aeruginosa to first-line antibiotics are <80%. 
Thus, when a septic patient with a high probability of P. aeruginosa 
infection is encountered in such settings, empirical combination 
therapy should be administered until the pathogen is identified 
and susceptibility data become available. Thereafter, whether one 
or two agents should be continued remains a matter of individual 
preference. Recent studies suggest that extended or continuous 
infusions of β-lactams such as cefepime, piperacillin-tazobactam, 
or meropenem may result in better outcomes of Pseudomonas bac­
teremia and possibly of Pseudomonas pneumonia. The duration of 
antibiotic therapy has now become an important consideration due 
to the increasing isolation of multiple drug-resistant (MDR) and 
extensively drug-resistant (XDR) P. aeruginosa strains. Recently 
published studies now strongly support the use of shorter courses of

therapy (7 days) rather than the longer duration (10−14 days) that 
is commonly recommended for many cases of Pseudomonas bacte­
remia. As in S. aureus bacteremia, catheter removal is important.

Acute Pneumonia 
Respiratory infections are the most common 
of all infections caused by P. aeruginosa. P. aeruginosa is common in 
both hospital-acquired pneumonia (HAP) and ventilator-associated 
pneumonia (VAP). This organism appears first or second among the 
causes of VAP. However, much debate centers on the actual role of 

P. aeruginosa in VAP. Many of the relevant data are based on cultures 
of sputum or endotracheal tube aspirates and may represent nonpatho­
genic colonization of the tracheobronchial tree, biofilms on the endo­
tracheal tube, or simple tracheobronchitis. The increasing use of PCR 
testing on endotracheal samples has further compounded this issue. 
PCR coupled with the widespread use of computed tomography with 
poor specificity for pneumonia, and overlap in appearance with fluid 
overload in patients with low to intermediate clinical suspicion, may 
contribute to the overdiagnosis of HAP and VAP. This scenario empha­
sizes the importance of clinical judgment in adjudicating P. aeruginosa 
colonization versus infection.
Older reports of P. aeruginosa pneumonia described patients with an 
acute clinical syndrome of fever, chills, cough, and necrotizing pneu­
monia indistinguishable from other gram-negative bacterial pneumo­
nias. The traditional accounts described a fulminant infection. Chest 
radiographs demonstrated bilateral pneumonia, often with nodular 
densities with or without cavities. This picture is now remarkably rare. 
Today, the typical patient is on a ventilator, has a slowly progressive 
infiltrate, and has been colonized with P. aeruginosa for days. While 
some cases may progress rapidly over 48–72 h, they are the exceptions. 
Nodular densities are not commonly seen. However, infiltrates may 
go on to necrosis. Necrotizing pneumonia has also been seen in the 
community (e.g., after inhalation of hot-tub water contaminated with 
P. aeruginosa). The typical patient has fever, leukocytosis, tachypnea, 
hypoxemia, and purulent sputum, and the chest radiograph shows a 
new infiltrate or the expansion of a preexisting infiltrate. A sputum 
Gram’s stain showing mainly polymorphonuclear leukocytes (PMNs) 
in conjunction with a culture positive for P. aeruginosa in this setting 
suggests a diagnosis of acute P. aeruginosa pneumonia.
PART 5
Infectious Diseases
There have been increasing reports of the occurrence of communityacquired P. aeruginosa pneumonia among patients with underlying 
lung diseases. While this undoubtedly occurs, it is difficult to make 
this diagnosis with a great degree of certainty with the use of sputum 
cultures in a population prone to airway colonization by multiple 
strains of bacteria. The patient population in whom the possibility of 
a community-acquired P. aeruginosa pneumonia should be considered 
is the neutropenic patient, given the pivotal role that neutrophils play 
in defense against this bacterium. Such a patient, whether hospitalized 
or admitted from the community with a pneumonia, should be treated 
empirically for P. aeruginosa.
TREATMENT
Acute Pneumonia
(Table 170-2) Therapy for P. aeruginosa pneumonia remains unsat­
isfactory. Reports suggest mortality rates of 40–80%, but how many 
of these deaths are attributable to underlying disease remains 
unknown. The drugs of choice for P. aeruginosa pneumonia are 
similar to those given for bacteremia. A potent antipseudomonal 
β-lactam drug is the mainstay of therapy. Failure rates were high 
when aminoglycosides were used as single agents, possibly because 
of their poor penetration into the airways and their binding to 
airway secretions. Nonetheless, for the treatment of patients at high 
risk of death, some experts suggest the combination of a β-lactam 
agent and an antipseudomonal fluoroquinolone or aminoglycoside. 
As for the duration of therapy, recent IDSA/American Thoracic 
Society (ATS) guidelines recommend 7 days of treatment for 
HAP or VAP, even when P. aeruginosa is the offending organism. 
However, the outcome in neutropenic patients is poor, especially 

if accompanied by bacteremia; thus, therapy needs to be extended 
until neutropenia resolves. In addition, therapy longer than 7 days 
should be used in patients with P. aeruginosa necrotizing pneumo­
nia as, functionally, this entity is similar to a lung abscess.
Chronic Respiratory Tract Infections 
P. aeruginosa is respon­
sible for chronic infections of the airways associated with a number 
of underlying or predisposing conditions—most commonly CF 
(Chap. 302). A state of chronic colonization beginning early in child­
hood is seen in some Asian populations with chronic or diffuse pan­
bronchiolitis, a disease of unknown etiology. P. aeruginosa is one of the 
organisms that colonizes damaged bronchi in bronchiectasis, a disease 
secondary to multiple causes in which profound structural abnormali­
ties of the airways result in mucus stasis.
TREATMENT
Chronic Respiratory Tract Infections
Optimal management of chronic P. aeruginosa lung infection has not 
been determined. Patients respond clinically to antipseudomonal 
therapy, but the organism is rarely eradicated. Because eradication is 
unlikely, the aim of treatment for chronic infection is to quell exac­
erbations of inflammation. The regimens used are similar to those 
used for pneumonia, but an aminoglycoside is almost always added 
because resistance is common in chronic disease. However, it may 
be more appropriate to use an inhaled aminoglycoside preparation 
in order to maximize airway drug levels. MDR strains are now com­
monly found in such patients given their increased life span and the 
repeated courses of antibiotics they receive.
Endovascular Infections 
Infective endocarditis of native valves 
due to P. aeruginosa is most commonly seen in those who use IV 
drugs. This organism has also been reported to cause prosthetic-valve 
endocarditis. Sites of prior native-valve injury due to the injection of 
foreign material such as talc or fibers probably serve as niduses for 
bacterial attachment to the heart valve. The manifestations of P. aeru­
ginosa endocarditis resemble those of other forms of endocarditis in 
those who use IV drugs except that the disease is more indolent than 

S. aureus endocarditis. While most disease involves the right side of 
the heart, left-sided involvement is not rare, and multivalvular disease 
is common. Fever is a common manifestation, as is pulmonary involve­
ment (due to septic emboli to the lungs). Thus, patients may also 
experience chest pain and hemoptysis. Involvement of the left side of 
the heart may lead to signs of cardiac failure, systemic emboli, and local 
cardiac involvement with sinus of Valsalva abscesses and conduction 
defects. Skin manifestations other than injection site infections are rare 
in this disease, and ecthyma gangrenosum is not common. Vertebral 
osteomyelitis and sternoclavicular joint septic arthritis are uncommon 
but pathognomic complications of this disease. The diagnosis is based 
on positive blood cultures along with clinical signs of endocarditis.
TREATMENT
Endovascular Infections
(Table 170-2) It has been customary to use synergistic antibiotic 
combinations in treating P. aeruginosa endocarditis because of the 
development of resistance during therapy with a single antipseudo­
monal β-lactam agent. Which combination therapy is preferable is 
unclear, as all combinations have failed. Treatment is likely to more 
often be successful in cases of right-sided endocarditis. Cases of 
P. aeruginosa endocarditis that relapse during or fail to respond to 
therapy are often caused by resistant organisms and may require 
surgical therapy. Other considerations for valve replacement are 
similar to those in other forms of endocarditis (Chap. 133).
Bone and Joint Infections 
P. aeruginosa is an infrequent cause 
of bone and joint infections. However, Pseudomonas bacteremia or

infective endocarditis caused by the injection of contaminated illicit 
drugs has been documented to result in vertebral osteomyelitis and 
sternoclavicular joint arthritis. The clinical presentation of vertebral 

P. aeruginosa osteomyelitis is more indolent than that of staphylococcal 
osteomyelitis. The duration of symptoms in IV drug users with verte­
bral osteomyelitis due to P. aeruginosa varies from weeks to months. 
Fever is not uniformly present; when present, it tends to be low grade. 
There may be mild tenderness at the site of involvement. Blood cul­
tures are usually negative unless there is concomitant endocarditis. The 
erythrocyte sedimentation rate (ESR) is generally elevated. Vertebral 
osteomyelitis due to P. aeruginosa has also been reported in the elderly, 
in whom it originates from urinary tract infections (UTIs). The infec­
tion generally involves the lumbosacral area because of a shared venous 
drainage (Batson’s plexus) between the lumbosacral spine and the pel­
vis. Sternoclavicular septic arthritis due to P. aeruginosa is seen almost 
exclusively in persons who use IV drugs. This disease may occur with 
or without endocarditis, and a primary site of infection often is not 
found. Plain radiographs show joint or bone involvement. Treatment 
of these forms of disease is generally successful.
Pseudomonas osteomyelitis of the foot most often follows punc­
ture wounds through sneakers and mostly affects children. The main 
manifestation is pain in the foot, sometimes with superficial cellulitis 
around the puncture wound and tenderness on deep palpation of the 
wound. Multiple joints or bones of the foot may be involved. Systemic 
symptoms are generally absent, and blood cultures are usually negative. 
Radiographs may or may not be abnormal, but the bone scan is usu­
ally positive, as are magnetic resonance imaging (MRI) studies. Needle 
aspiration usually yields a diagnosis. Prompt surgery, with exploration 
of the nail puncture tract and debridement of the involved bones and 
cartilage, is generally recommended in addition to antibiotic therapy.
Osteomyelitis due to P. aeruginosa is also seen following trauma and 
with decubitus ulcers. In these settings, the cause of osteomyelitis is 
often polymicrobial, and the role of P. aeruginosa can be questioned. 
It is therefore critical that deep bone biopsies be requested to ascertain 
its significance prior to starting treatment that targets P. aeruginosa.
TREATMENT
Bone and Joint Infections
The treatment of bone and joint infections due to P. aeruginosa is often 
governed by the primary Pseudomonas infection. Since endocarditis is 
often the primary infection, the agents used for endocarditis will dic­
tate treatment. In other situations, a 6-week course of therapy with an 
antipseudomonal β-lactam is recommended, and in case of puncturewound osteomyelitis, oral ciprofloxacin may be used.
Central Nervous System (CNS) Infections 
CNS infections due 
to P. aeruginosa are relatively rare. Involvement of the CNS is almost 
always secondary to a surgical procedure, head trauma, implanted 
devices, temporary external ventricular drains, and rarely bacteremia. 
The entity seen most often is postoperative or posttraumatic meningi­
tis. Subdural or epidural infection occasionally results from contamina­
tion of these areas. Embolic disease arising from endocarditis in users 
of IV drugs and leading to brain abscesses has also been described. The 
cerebrospinal fluid (CSF) profile of P. aeruginosa meningitis is no dif­
ferent from that of pyogenic meningitis of any other etiology.
TREATMENT
Central Nervous System Infections
(Table 170-2) Treatment of Pseudomonas meningitis is difficult; 
little information has been published. However, the general prin­
ciples involved in the treatment of meningitis apply, including 
the need for high doses of bactericidal antibiotics to attain high 
drug levels in the CSF. The agent with which there is the most 
published experience in P. aeruginosa meningitis is ceftazidime, 
but other antipseudomonal β-lactam drugs that attain reasonable 
CSF concentrations, such as cefepime, piperacillin/tazobactam, and 

meropenem, have also been used successfully. Other forms of 

P. aeruginosa CNS infection, such as brain abscesses and epidural 
and subdural empyema, generally require surgical drainage and 
removal of devices, in addition to antibiotic therapy.

Eye Infections 
Eye infections due to P. aeruginosa occur mainly 
as a result of direct inoculation into the tissue during trauma or sur­
face injury by contact lenses. Keratitis and corneal ulcers are the most 
common types of eye disease and are often associated with contact 
lenses (especially the extended-wear variety). Keratitis can be slowly 
or rapidly progressive, but the classic description is disease progress­
ing over 48 h to involve the entire cornea, with opacification and 
sometimes perforation. P. aeruginosa keratitis should be considered a 
medical emergency because of the rapidity with which it can progress 
to loss of sight. P. aeruginosa endophthalmitis secondary to bacteremia 
is the most devastating of P. aeruginosa eye infections. The disease is 
fulminant, with severe pain, chemosis, decreased visual acuity, anterior 
uveitis, vitreous involvement, and panophthalmitis. It is also a rare 
complication of cataract removal with lens insertion. In the United 
States, a recent outbreak associated with artificial tears with carbape­
nem-resistant P. aeruginosa led to serious eye infections and, in some 
cases, vision loss, enucleation, or death.
TREATMENT
Eye Infections
(Table 170-2) The usual therapy for keratitis is the administration 
of topical antibiotics. Therapy for endophthalmitis includes the use 
of high-dose local and systemic antibiotics (to achieve higher drug 
concentrations in the eye) and vitrectomy.
CHAPTER 170
Ear Infections 
P. aeruginosa infections of the ears vary from mild 
swimmer’s ear to serious life-threatening infections with neurologic 
sequelae. Swimmer’s ear is common among children and results from 
infection of moist macerated skin of the external ear canal. Most cases 
resolve with treatment, but some patients develop chronic drainage. 
Swimmer’s ear is managed with topical antibiotic agents (otic solu­
tions). The use of hearing aids may also predispose to this type of infec­
tion. The most serious form of Pseudomonas infection involving the 
ear has been given various names: two of these designations, malignant 
otitis externa and necrotizing otitis externa, are now used for the same 
entity. This disease was originally described in elderly patients with 
diabetes, in whom the majority of cases still occur. However, it has also 
been described in patients with AIDS and in elderly patients without 
underlying diabetes or immunocompromise. The usual presenting 
symptoms are decreased hearing and ear pain, which may be severe 
and lancinating. The pinna is usually painful, and the external canal 
may be tender. The ear canal almost always shows signs of inflamma­
tion, with granulation tissue and exudate. Tenderness anterior to the 
tragus may extend as far as the temporomandibular joint and mastoid 
process. A small minority of patients have systemic symptoms. Patients 
in whom the diagnosis is made late may present with cranial nerve 
palsies, most commonly cranial nerve VII, or even with cavernous 
venous sinus thrombosis. The ESR is invariably elevated (≥100 mm/h). 
The diagnosis is made on clinical grounds in severe cases; however, 
the “gold standard” is a positive technetium-99 bone scan in a patient 
with otitis externa due to P. aeruginosa. In diabetic patients, a positive 
bone scan constitutes presumptive evidence for this diagnosis and 
should prompt biopsy or empirical therapy. However, it should be kept 
in mind that S. aureus and Aspergillus spp. can also cause this entity.
Infections Due to Pseudomonas, Burkholderia, and Stenotrophomonas Species
TREATMENT
Ear Infections
(Table 170-2) Given the infection of the ear cartilage, sometimes 
with mastoid or petrous ridge involvement, patients with malignant 
(necrotizing) otitis externa are treated as for osteomyelitis.

Urinary Tract Infections 
UTIs due to P. aeruginosa generally 
occur as a complication of a catheter in the urinary tract, an obstruc­
tion or stone in the genitourinary system, urinary tract instrumenta­
tion, or surgery. A P. aeruginosa UTI occurring in the community often 
signals the presence of an abnormality in the urinary tract. It has been 
reported that the urinary tract is the second most important site of 
infection leading to Pseudomonas bacteremia.

TREATMENT
Urinary Tract Infections
(Table 170-2) Most P. aeruginosa UTIs are considered complicated 
infections that must be treated longer than uncomplicated cystitis. 
In general, a 7- to 10-day course of treatment suffices. Urinary cath­
eters, stents, or stones should be removed to prevent relapse, which 
is common and may not be due to antibiotic resistance but rather to 
factors such as a foreign body that has been left in place or an ongo­
ing obstruction. Removal of a urinary catheter will allow shorter 
courses of antibiotic therapy if that is the only predisposing factor.
Skin and Soft Tissue Infections 
Besides pyoderma (ecthyma) 
gangrenosum in neutropenic patients, folliculitis and other papular or 
vesicular lesions due to P. aeruginosa have been extensively described 
and are collectively referred to as dermatitis. Multiple outbreaks have 
been linked to whirlpools, spas, and swimming pools. To prevent such 
outbreaks, the growth of P. aeruginosa in the home and in recreational 
environments must be controlled by proper chlorination of water. Most 
cases of hot-tub folliculitis are self-limited, requiring only the avoid­
ance of exposure to the contaminated source of water. Approximately 
one-third of reported outbreaks are associated with hotel facilities. 
Patients may also have ear pain, skin rashes, and eye irritation.
PART 5
Infectious Diseases
Toe-web infections occur especially often in the tropics, and the 
“green-nail syndrome” is caused by P. aeruginosa paronychia, which 
results from frequent submersion of the hands in water. In the latter 
entity, the green discoloration results from diffusion of pyocyanin into 
the nail bed. P. aeruginosa remains a prominent cause of burn wound 
infections in some parts of the world. The management of these infec­
tions is best left to specialists in burn wound care.
Infections in Febrile Neutropenic Patients 
In febrile neutro­
penia, P. aeruginosa has historically been the organism against which 
empirical coverage is always essential. Although in Western countries 
these infections are now less common, their importance has not 
diminished because of persistently high mortality rates. In other parts 
of the world, P. aeruginosa continues to be a significant problem in 
febrile neutropenia, causing a larger proportion of infections in febrile 
neutropenic patients than any other single organism. For example, 

P. aeruginosa was responsible for 28% of documented infections in 499 
febrile neutropenic patients in one study from the Indian subcontinent 
and for 31% of such infections in another. In a large study of infections 
in leukemia patients from Japan, P. aeruginosa was the most frequently 
documented cause of bacterial infection. In studies performed in 
North America, northern Europe, and Australia, the incidence of 

P. aeruginosa bacteremia in febrile neutropenia was quite variable. In a 
review of 97 reports published between 1987 and 1994, the incidence 
was reported to be 1–2.5% among febrile neutropenic patients given 
empirical therapy and 5–12% among patients with microbiologi­
cally documented infections. The most common clinical syndromes 
encountered were bacteremia, pneumonia, and soft tissue infections 
manifesting mainly as ecthyma gangrenosum.
TREATMENT
Infections in Febrile Neutropenic Patients
(Table 170-2) Compared with rates three decades ago, improved 
rates of response to antibiotic therapy have been reported in many 
studies. A study of 127 patients demonstrated a reduction in the 
mortality rate from 71 to 25% with the introduction of ceftazidime 

and imipenem. Because neutrophils—the normal host defenses 
against this organism—are absent in febrile neutropenic patients, 
maximal doses of antipseudomonal β-lactam antibiotics should be 
used for the management of P. aeruginosa bacteremia in this setting.
Infections in Patients with AIDS 
P. aeruginosa infections were 
well documented in patients with AIDS before the advent of antiret­
roviral therapy. Since the introduction of protease inhibitors, P. aeru­
ginosa infections in patients with AIDS have been seen less frequently 
but still occur, particularly in the form of sinusitis. While this entity is 
now uncommon in developed nations, there are still large numbers of 
patients with untreated HIV infection or poorly controlled disease in 
developing nations who are likely to suffer from P. aeruginosa infec­
tions. The clinical presentation of Pseudomonas infection (especially 
pneumonia and bacteremia) in patients with AIDS is remarkable in 
that, although the illness may appear not to be severe, the infection may 
nonetheless be fatal. Patients with bacteremia may have only a lowgrade fever and may present with ecthyma gangrenosum. Pneumonia, 
with or without bacteremia, is perhaps the most common type of 

P. aeruginosa infection. Patients with P. aeruginosa pneumonia exhibit 
the classic clinical signs and symptoms of pneumonia, such as fever, 
productive cough, and chest pain. The infection may be lobar or mul­
tilobar and shows no predisposition for any particular location. The 
most striking feature is the high frequency of cavitary disease.
TREATMENT
Infections in Patients with AIDS
Therapy for any of these conditions in AIDS patients is no different 
from that in other patients. However, relapse is the rule unless the 
patient’s CD4+ T-cell count rises to >50/μL or suppressive antibiotic 
therapy is given. In attempts to achieve cures and prevent relapses, 
therapy tends to be more prolonged.
Gastrointestinal Infections 
A poorly understood syndrome 
caused by P. aeruginosa has been described in the Far East and has been 
called Shanghai fever and Pseudomonas enterocolitis. This syndrome 
occurs in young children; its occurrence in adults appears to be rare. 
Shanghai fever manifests as severe enteric disease, sepsis with inva­
sive disease, and complications, whereas Pseudomonas enterocolitis 
is characterized by prolonged fever with bloody or mucoid diarrhea 
mimicking bacterial enterocolitis. The mortality rate ranges between 
23 and 89%, with ecthyma gangrenosum occurring in >50% of cases. 
Early recognition and treatment have led to a reduction in the mortal­
ity rate. There is an above-average occurrence of the exoU gene among 
Pseudomonas isolates from patients with this syndrome.
Multidrug-Resistant Infections 
(Table 170-2) P. aeruginosa has 
a notorious propensity to develop antibiotic resistance. Over three 
decades, the impact of resistance was minimized by the rapid develop­
ment of several potent antipseudomonal β-lactams and fluoroquino­
lones. However, rates of resistance to these agents that revolutionized 
the treatment of P. aeruginosa have risen to the point where some are 
almost unusable empirically because of the worldwide emergence of 
strains carrying determinants that mediate resistance. Extremely high 
rates of MDR strains have been reported from eastern and southern 
Europe, Latin America, India, and China, especially in ICUs. Physi­
cians have had to resort to drugs such as colistin and polymyxin B, 
which were discarded decades ago. This surge in resistance is mediated 
by multiple mechanisms sometimes converging in individual strains. 
Chief among these are chromosomal or plasmid-borne penicillinases, 
extended-spectrum β-lactamases, cephalosporinases, and carbapen­
emases. Any of these may be combined with permeability mutations 
and efflux pump overexpression. The greatest nemesis in this regard is 
the worldwide presence of carbapenemases in P. aeruginosa leading to 
resistance to most β-lactams except some of the newest agents recently 
developed. These new agents are generally combinations of a cephalo­
sporin or a carbapenem most often with a novel β-lactamase inhibitor. 
Several have been approved for clinical use, and all are active against

MDR P. aeruginosa to varying degrees. Currently approved agents 
include ceftolozane-tazobactam, ceftazidime-avibactam, meropenemvaborbactam, and imipenem-relebactam. A novel cephalosporin, 
cefiderocol, which uses the iron uptake pathway of P. aeruginosa, also 
demonstrates activity against MDR strains. Since MDR and XDR 

P. aeruginosa are unpredictable in regard to the underlying mecha­
nisms of resistance, laboratory testing is absolutely required before the 
use of any of these agents. Most academic institutions restrict the use of 
these agents as there are increasing reports of resistance even to these 
agents, as well the cost implications of misuse.
BURKHOLDERIA SPECIES
■
■BURKHOLDERIA CEPACIA COMPLEX
The B. cepacia complex (BCC) gained notoriety as the cause of a rap­
idly fatal syndrome of respiratory distress and septicemia (the “cepacia 
syndrome”) in CF patients. Of the more than 20 species of this com­
plex, the three most frequently seen in CF patients are B. cenocepacia, 
B. multivorans, and B. stabilis. In addition to their occurrence in CF, 
members of this complex were not uncommonly encountered in ICU 
patients (previously designated Pseudomonas cepacia) and patients 
with chronic granulomatous disease, in whom they caused lung dis­
ease. BCC organisms are environmental organisms that inhabit moist 
environments and are found in the rhizosphere. They possess multiple 
virulence factors that may play roles in disease as well as colonizing 
factors that are capable of binding to lung mucus—an ability that may 
explain the predilection of B. cepacia for the lungs in CF. B. cenocepacia 
is motile, secretes elastase, and possesses components of an injectable 
toxin-secretion system like that of P. aeruginosa; its LPS is among the 
most potent of all LPSs in stimulating an inflammatory response in 
the lungs. Inflammation may be the major cause of the lung disease 
seen in the “cepacia” syndrome. Besides infecting the lungs in CF, the 
BCC organisms appear as airway colonizers during broad-spectrum 
antibiotic therapy and are causes of VAP, catheter-associated infections, 
and wound infections. B. cenocepacia has emerged as a barrier to lung 
transplantation in CF, with relatively high mortality rates after a year 
compared to infection with other members of this complex.
TREATMENT
B. cepacia Complex Infections
BCC organisms are intrinsically resistant to many antibiotics, ren­
dering empiric treatment difficult. Therefore, treatment must be 
tailored according to sensitivities. Trimethoprim-sulfamethoxazole 
(TMP-SMX), meropenem, and minocycline are the most active 
agents in vitro and may be started as first-line agents (Table 170-2). 
However, recent reports indicate that there has been increasing 
resistance to these agents especially in CF patients. Some strains are 
susceptible to third-generation ureidopenicillins, advanced cepha­
losporins, and fluoroquinolones, and these agents may be used 
against isolates known to be susceptible. Newer antibiotics such 
as ceftolozane-tazobactam and ceftazidime-avibactam show good 
activity against MDR strains in vitro. However, there is very limited 
clinical experience with these agents.
■
■BURKHOLDERIA PSEUDOMALLEI
B. pseudomallei is the causative agent of melioidosis, a disease of 
humans and animals that is geographically restricted to Southeast 
Asia and northern Australia, with occasional cases in countries such 
as India and China. This organism may be isolated from individuals 
returning directly from these endemic regions and from military per­
sonnel who have served in endemic regions. Symptoms of this illness 
may develop only at a later date because of the organism’s ability to 
cause latent infections, which has been attributed to its ability to sur­
vive within cells. B. pseudomallei is found in soil and water. Humans 
and animals are infected by inoculation, inhalation, or ingestion; only 
rarely is the organism transmitted from person to person. Humans 
are not colonized without being infected. Among the pseudomonads, 

B. pseudomallei is perhaps the most virulent species. Host compromise 
is not an essential prerequisite for disease, although many patients have 
common underlying medical diseases (e.g., diabetes, renal failure, or 
alcohol abuse). B. pseudomallei is a facultative intracellular organism 
whose replication in PMNs and macrophages may be aided by the 
possession of a polysaccharide capsule. The organism also possesses 
elements of a type III secretion system that plays a role in its intracel­
lular survival. During infection, there is a florid inflammatory response 
whose role in disease is unclear.

B. pseudomallei causes a wide spectrum of conditions, ranging from 
asymptomatic infection to abscesses, pneumonia, and disseminated 
disease. It is a significant cause of fatal community-acquired pneu­
monia and septicemia in endemic areas, with mortality rates as high 
as 44% reported in Thailand. Acute pulmonary infection is the most 
commonly diagnosed form of melioidosis. Pneumonia may be asymp­
tomatic (with routine chest radiographs showing mainly upper-lobe 
infiltrates) or may present as severe necrotizing disease. B. pseudom­
allei also causes chronic pulmonary infections with systemic mani­
festations that mimic those of tuberculosis, including chronic cough, 
fever, hemoptysis, night sweats, and cavitary lung disease. Besides 
pneumonia, the other principal form of B. pseudomallei disease is skin 
ulceration with associated lymphangitis and regional lymphadenopa­
thy. Spread from the lungs or skin, which is most often documented 
in debilitated individuals, gives rise to septicemic forms of melioidosis 
that carry a high mortality rate.
TREATMENT
B. pseudomallei Infections
CHAPTER 170
B. pseudomallei is susceptible to advanced penicillins, cephalosporins, 
and carbapenems (Table 170-2). Treatment is divided into two stages: 
an intensive 2-week phase of therapy with ceftazidime or a carbape­
nem followed by at least 12 weeks of oral TMP-SMX to eradicate the 
organism and prevent relapse. Australian guidelines for treating this 
condition recommend longer periods of intensive therapy—4−8 weeks 
for severe infections, osteomyelitis, and CNS infections. The recogni­
tion of this bacterium as a potential agent of biologic warfare has 
stimulated interest in the development of a vaccine.
Infections Due to Pseudomonas, Burkholderia, and Stenotrophomonas Species
■
■BURKHOLDERIA MALLEI
B. mallei causes the equine disease glanders in Africa, Asia, and South 
America. The organism was eradicated from Europe and North America 
decades ago. The last case seen in the United States occurred in 2001 in a 
laboratory worker; before that, B. mallei had last been seen in this coun­
try in 1949. In contrast to the other organisms discussed in this chapter, 
B. mallei is not an environmental organism and does not persist outside 
its equine hosts. Consequently, B. mallei infection is an occupational 
risk for handlers of horses, equine butchers, and veterinarians in areas 
of the world where it still exists. Diabetics are thought to be especially 
susceptible to infection by this organism. The polysaccharide capsule 
is a critical virulence determinant. The organism is transmitted from 
animals to humans by inoculation into the skin, where it causes local 
infection with nodules and lymphadenitis. Regional lymphadenopathy 
is common. Respiratory secretions from infected horses are extremely 
infectious. Inhalation results in clinical signs of typical pneumonia but 
may also cause an acute febrile illness with ulceration of the trachea. The 
organism may disseminate from the skin or lungs to cause septicemia 
with signs of sepsis. The septicemic form is frequently associated with 
shock and a high mortality rate. The infection may also enter a chronic 
phase and present as disseminated abscesses. B. mallei infection may 
present as early as 1–2 days after inhalation or (in cutaneous disease) 
may not become evident for months.
TREATMENT
B. mallei Infections
The antibiotic susceptibility pattern of B. mallei is similar to that 
of B. pseudomallei; in addition, the organism is susceptible to the