There is a wide variety of diseases that may be caused by PI. At this point, some of the more frequently detected symptoms of PI shall be presented.

• Pneumonia due to PI most likely occurs in AIDS patients and individuals that are otherwise severely immunocompromised. There is a strong relation between this disease and use of endotracheal tubes and respiratory support.
• Urinary tract PI may be detected after respective surgical interventions or prolonged use of a urinary catheter. Also, urinary tract obstruction increases the risk for PI.
• Otitis externa is most commonly associated with ear pain and itching in the external auditory channel. Otorrhea may be observed. Since this disease often develops in patients whose ears are in frequent contact with water, it is also caused swimmer's ear. In immunodeficient patients, particularly in diabetics, malignant otitis externa may develop. Here, P. aeruginosa spreads to adjacent soft and osseous tissues and causes severe inflammation and potentially cranial nerve damage. Symptoms comprise pain, ill-smelling discharge and cranial nerve palsies. If the latter develop or if the disease is not adequately treated, it may lead to death.
• Keratitis. PI may account for severe corneal ulcers because proteases released by Pseudomonas species damage superficial cornea layers and facilitate invasion of deeper ones. Contaminated contact lenses and contact lens solutions are one of the main sources of infection.
• Skin and soft tissue infections often result from wound infections whereas Pseudomonas folliculitis, also termed hot tub folliculitis, has a pathogenesis similar to that of otitis externa. With regards to wound infections, patients may have stepped on a nail that subsequently perforated their sole and enabled PI of skin, fat, tendons and muscles. Osteochondritis and osteomyelitis may develop. Also, skin lesions resulting from burns, cuts or surgery may become infected with Pseudomonas. Wound fluids are typically greenish and have a fruity smell. In elderly and immunocompromised patients whose hemogram usually reveals neutropenia, PI of the skin may result in ecthyma gangrenosum. This kind of severe skin infection is characterized by a necrotic center and can often be found in moist areas, i.e., in armpits and anogenital regions.
• Septicemia may result from any of the aforementioned conditions, but mainly affects patients with severe infections and a weakened immune system or underlying diseases. In some cases, bacteria may directly reach the blood stream. This may be the case if an intravenous access is established, e.g., within the scope of medical treatment, but more frequently to administer illegal drugs. Possible consequences of septicemia are endocarditis and meningitis as well as spread to any of the aforementioned organ systems.

• Inflammation

  RATIONALE: Patients with cystic fibrosis (CF) lung disease have chronic airway inflammation driven by disrupted balance of T-cell (Th17 and Th2) responses. [ncbi.nlm.nih.gov]

  It is defined as inflammation of this layer due to infection. It occurs mostly secondary from other infected sites. Most of the time, it also affects the valves of the heart leading to heart attack. [icliniq.com]

• Fever

  Pus discharge and mild fever may accompany this. If it remains untreated it will spread to central nervous system leading to meningitis, abscess and brain nerve palsy. [icliniq.com]

  Pseudomonas bacteremia resembles other bacteremias, producing fever, tiredness, muscle pains, joint pains, and chills. Bone infections are marked by swelling, redness, and pain at the infected site and possibly fever. [medical-dictionary.thefreedictionary.com]

  Shanghai fever is an enteritis manifestation of a pseudomonal infection, which presents with headache, fever, exhaustion, enlargement of the spleen, rose spots, and dehydration [3]. [microbewiki.kenyon.edu]

  If you run a fever, have pain or see redness or discharge at your surgery site, call your doctor right away. [webmd.com]

• High Fever

  A serious infection can cause symptoms of high fever, chills, confusion, and shock. How is an infection treated? Antibiotics are the main treatment. Usually two different kinds are used. [northshore.org]

• Aspiration

  Although organisms can be occasionally cultured from aspirated vitreous fluid, the diagnosis is established most frequently from blood cultures [ 7, 9 ]. In our case aspiration of vitreous fluid was not performed. [casesjournal.biomedcentral.com]

  As Pseudomonas aeruginosa can be recovered from the oral cavity of ∼4% of healthy individuals 7, it is therefore possible that some of these bacteria are aspirated into the dental chair unit waterlines through a defective check valve and are able to colonise [erj.ersjournals.com]

  […] hospital acquired urinary-tract infections; rarely causes community acquired infections in immunocompetent patients HOST RANGE: Humans, animals, plants INFECTIOUS DOSE: Not known MODE OF TRANSMISSION: Direct contact with contaminated water, aerosols or aspirations [forum.desprecopii.com]

  Persistent drainage encouraged a return to the operating room for exploration of the wound, irrigation and debridement of the suprafascial layers, and cultures of the superficial layers (via cotton swabs) and the hip joint (via needle aspiration). [healio.com]

• Tachypnea

  This may cause them to have a chronic, phlegm-producing cough, loss of appetite, weight loss, wheezing and a fast breathing rate (tachypnea). [health.howstuffworks.com]

  […] motion; neurologic deficits Eye infections: Lid edema, conjunctival erythema and chemosis, and severe mucopurulent discharge Malignant otitis externa: Erythematous, swollen, and inflamed external auditory canal; local lymphadenopathy Bacteremia: Fever, tachypnea [emedicine.medscape.com]

• Chronic Cough

  Chronic cough, airway obstruction, and infections that come and go and cause damage to the bronchi and bronchioles are characteristic of bronchiectasis, leaving people with this disease susceptible to serious infections with bacterial pathogens and fungal [bronchiectasisnewstoday.com]

  The characteristic symptoms are chronic cough, hypersecretion of the mucus, high grade fever, weakness, etc. Blood Stream - Pseudomonas causes bacteremia, which is the presence of Pseudomonas aeruginosa in blood. [icliniq.com]

• Productive Cough

  Nosocomial infections by P. aeruginosa are particularly common in intensive care units and can lead to fatal pneumonia in which the patient has a productive cough, chills, breathing difficulties and cyanosis. [microbiologybook.org]

  P. aeruginosa pneumonia is marked by chills, fever, productive cough, difficult breathing, and blue-tinted skin. [medical-dictionary.thefreedictionary.com]

  Blood infections are characterized by fever, chills, fatigue, muscle and joint pains, and are extremely serious. [4] Lung infections (pneumonia) include symptoms like chills, fever, a productive cough, difficulty breathing. [5] Skin infections may cause [wikihow.com]

• Abdominal Distension

  Abnormal abdominal distension and abdominal pain is also present. Urinary Tract - This organism causes infection of the ascending urinary tract. It is initiated by the catheterization or surgery. [icliniq.com]

  Pseudomonas spp. typhlitis most often occurs in patients with neutropenia and presents with a sudden onset of fever, abdominal distension and increasing abdominal pain. [patient.info]

  Typhlitis is most common in patients with neutropenia as a result of acute leukemia, which presents with sudden fever, abdominal distension, and abdominal pain. [microbewiki.kenyon.edu]

• Nausea

  Gastrointestinal Tract - Irritability, nausea, diarrhea, dehydration are the common complications associated with this organism. Abnormal abdominal distension and abdominal pain is also present. [icliniq.com]

  Bloodstream infections can cause various symptoms, including: Fever and chills Body aches Light-headedness Rapid pulse and breathing Nausea and vomiting Diarrhea Decreased urination Pneumonia can cause: Fever and chills Difficulty breathing Cough, sometimes [everydayhealth.com]

  […] such as shaking chills and fever (>104 degrees F), shortness of breath, rapid breathing (more than 30 breaths/min.) and heartbeat(>20 bpm) chest pain that occurs on the infected side only, muscle aches, a dry cough at first then sputum develops later, nausea [austincc.edu]

• Vomiting

  Bloodstream infections can cause various symptoms, including: Fever and chills Body aches Light-headedness Rapid pulse and breathing Nausea and vomiting Diarrhea Decreased urination Pneumonia can cause: Fever and chills Difficulty breathing Cough, sometimes [everydayhealth.com]

  Vomiting only twice. Yesterday, I was prescribed Levofloxacin 500 mg for four days. Now, after 24 hours of taking the first pill, there is no improvement. Diarrhea is 20 times a day very watery. I take electrolytes and lots... Read Full » Dr. [icliniq.com]

  […] shaking chills and fever (>104 degrees F), shortness of breath, rapid breathing (more than 30 breaths/min.) and heartbeat(>20 bpm) chest pain that occurs on the infected side only, muscle aches, a dry cough at first then sputum develops later, nausea, and vomiting [austincc.edu]

  Young infants who may contract the disease in a nursery epidemic may present symptoms of irritability, vomiting, diarrhea, and dehydration. [microbewiki.kenyon.edu]

• Cyanosis

  Nosocomial infections by P. aeruginosa are particularly common in intensive care units and can lead to fatal pneumonia in which the patient has a productive cough, chills, breathing difficulties and cyanosis. [microbiologybook.org]

  […] and nature of the infection, as follows: Endocarditis: Fever, murmur, and positive blood culture findings; peripheral stigmata such as Roth spots, Janeway lesions, Osler nodes, splinter hemorrhages, and splenomegaly Pneumonia: Rales, rhonchi, fever, cyanosis [emedicine.medscape.com]

• Hypertension

  He had no previous ulceration and his only known comorbidity was well-controlled hypertension. On examination, his peripheral pulses were weak and he had a severe loss of foot sensation bilaterally. [cmaj.ca]

• Confusion

  A serious infection can cause symptoms of high fever, chills, confusion, and shock. How is an infection treated? Antibiotics are the main treatment. Usually two different kinds are used. [northshore.org]

  Fever, headache, confusion, loss of memory are the main features of it. Ear - This organism causes otitis externa, a fungal infection of the external ear. It is characterized by pus formation, intense pain and swelling of the inner ear. [icliniq.com]

  This skin disorder is called pseudomonas or "hot tub" folliculitis, and is often confused with chickenpox. Severe skin infection may occur in patients with P. aeruginosa bacteremia. [medical-dictionary.thefreedictionary.com]

Bacteria need to be isolated from samples obtained from the infected site, i.e., from sputum, urine, wound fluids etc. In order to rule out septicemia, blood samples should also be analyzed for the presence of Pseudomonas or Burkholderia species.

It is highly recommended to establish an antibiogram.

Additionally, samples should be taken from possible sources of infection. Findings may help to end exposure of the current patient and to avoid infecting other patients, e.g., by administering contaminated batches of therapeutic formulations.

• Hypogammaglobulinemia

  Neutropenia (ANC 3 ), hypogammaglobulinemia and steroid use (>1 mg/kg) were not significantly associated with recurrent infection. [nature.com]

  Acquired immunodeficiency in forms of hypogammaglobulinemia, neutropenia, complement deficiency, AIDS and iatrogenic immunosuppression also augments the risk for PI. [symptoma.com]

While carbapenems, third-generation cephalosporins, aminoglycosides, quinolones and colistin are often effective to treat PI, these bacteria tend to present several antimicrobial resistances. Serious infections should thus be treated with any combination of these antibiotics, but therapy may need to be readjusted as soon as the antibiogram is available.

In case of pneumonia, high local concentrations of antimicrobials may be reached by applying nebulized antimicrobials. Such therapy has been proposed for cystic fibrosis patients, but its superiority to systemic treatment has not yet been proven [5] [6].

Antibiotic therapy of PI should generally be administered systemically, but mild forms of keratitis may initially be treated topically. If bacteria invade deeper layers of the cornea or even additional ocular structures, systemic and possibly intraocular treatment is necessary.

Ceftazidime is highly recommended to treat Pseudomonas meningitis, because the drug accumulates in the subarachnoid space.

Surgical interventions may become necessary and wound debridement is one of the mainstays of therapy of pseudomonal skin infections [7]. Formation of gangrene should by all means be avoided [8]. Also, in order to cure cases of malignant otitis externa, aggressive, long-term antibiotic therapy often needs to be supplemented by surgical removal of necrotic tissue [9].

While localized infections, isolation of bacteria and timely initiation of treatment according to an antibiogram are associated with a good prognosis, there are several factors related to an unfavorable outcome. In this line, any sign of spread of infection, development of metastatic foci, neutropenia, leukocytopenia and septic shock worsen the patient's prognosis. If patients are treated with antimicrobials the causative agents are resistant to, the probability of septicemia and the aforementioned conditions increases.

Additionally, prognosis may highly depend on the progress of any underlying disease.

In total, far more than 100 Pseudomonas and Burkholderia species have been described. Only few species are human pathogens, others may cause diseases in animals and plants. Some of these bacteria are zoonotic agents, e.g., B. mallei, but the vast majority of germs pertaining to these genera are free-living organisms that prefer humid or even aqueous environments. Such is the case for P. aeruginosa, the most frequent causative agent of PI.

P. aeruginosa infections account for a significant share of nosocomial infections. Almost one out of ten nosocomial infections is caused by this bacterium and incidence rates have been reported to increase during the first decade of the 21st century [1]. It may trigger a wide variety of pathological conditions including pneumonia, infections of the gastrointestinal/urinary tract and the skin, and septicemia.

This pathogen is one of the most frequently isolated agents in cases of pneumonia, urinary tract infections, otitis externa and otitis media, keratitis and endocarditis. Cystic fibrosis patients are particularly susceptible for P. aeruginosa-mediated pneumonia. In immunodeficient patients or individuals presenting severe comorbidities, potentially life-threatening diseases such as malignant otitis externa and cerebral abscess may develop upon infection with P. aeruginosa .

B. cepacia is also related with nosocomial infections and the patient group with highest risk for B. cepacia infection is again the one suffering from cystic fibrosis. The bacterium may cause lethal necrotizing pneumonia and septicemia. There seem to be different strains that display distinct epidemiologic behavior.

B. mallei is a zoonotic agent and causes glanders. Although eradicated in many countries of the Western world, animals, particularly equids, in Africa, Middle East and Asia, but also in Central and South America, still carry the pathogen. Humans that contract the disease usually work closely with these animals or have been in contact with contaminated objects. The disease may eventually be re-imported to Europe or Northern America with infected animals.

B. pseudomallei is the causative agent of melioidosis, a disease that may be associated with pneumonia, lung abscess formation and pleural effusion. Most cases are reported in South-East Asia and Australia, but Africa, the Middle East and India are also endemic regions.

Age, gender and racial distribution differ between the above mentioned bacterial species. P. aeruginosa-mediated endocarditis, for instance, is more often seen in men than in women and preferentially affects blacks. Patients suffering from this disease have a mean age of 29 years. Also, PI may reflect the epidemiology of any underlying disease. Cystic fibrosis manifests early and pseudomonal pneumonia can often be detected in young infants; malignant otitis externa more frequently affects diabetic and immunodeficient elder people.

As has been indicated before, P. aeruginosa is an opportunistic pathogen that can frequently be isolated from healthy individuals. Immunodeficiency strongly facilitates tissue invasion and symptom onset. An endotracheal tube, a urinary catheter or an intravenous access as well as other artificial entries into the human body bear the risk of Pseudomonas infection. This risk is increased in patients suffering from hereditary disorders that affect their immune system, e.g., cystic fibrosis [2]. Acquired immunodeficiency in forms of hypogammaglobulinemia, neutropenia, complement deficiency, AIDS and iatrogenic immunosuppression also augments the risk for PI.

P. aeruginosa releases proteases that facilitate tissue invasion and finally septicemia, and toxins such as exotoxin A that interfere with host cell metabolism [3]. Septicemia is usually only observed in severely immunocompromised patients, but may lead to pneumonia, endocarditis, meningitis and death. While not directly related to pathogenesis of PI, efflux pumps detected in P. aeruginosa hinder antibiotics to accumulate in these bacteria and thus mediate resistances.

B. cepacia has first been described more than 60 years ago [4] and has subsequently been confirmed to account for numerous nosocomial infections of lungs, urinary tract and skin. Similar to what has been described for P. aeruginosa infection, there seems to be a strong association between use of endotracheal tubes and catheters and P. cepacia infection. Today, B. cepacia-triggered pneumonia and septicemia is a major concern in cystic fibrosis patients.

B. mallei is primarily an animal pathogen and transmission to humans presumably requires close contact to infected equids. Bacteria may invade the human body through oronasal mucosa or skin lesions. The infection may or may not distribute throughout the whole body via lymphatic and blood vessels. Mild cases of glanders consist in localized infections, while more severe forms compromise other organ systems or trigger lethal septicemia.

Similar symptoms may be caused by infection with B. pseudomallei. Although this pathogen has been isolated from a variety of animal species, humans most likely contract the disease when entering in contact with contaminated water or soil. As has been stated for B. mallei, this bacterium may account for superficial, localized infections, septicemia and formation of multiple abscesses.

Because PI are often nosocomial infections, adequate hygiene measures in hospitals may significantly contribute to reduce disease incidence. Endotracheal tubes, urinary catheters and similar equipment should not be used longer than absolutely necessary, particularly in immunodeficient patients. Prophylactic antibiotic treatment may generate resistances in Pseudomonas and Burkholderia strains and is therefore not recommended [10].

Contact to animals infected with B. mallei or B. pseudomallei should be avoided.

Bacteria pertaining to the genera of Pseudomonas or Burkholderia, formerly also classified as Pseudomonas, may cause Pseudomonas infection (PI). These rod-shaped bacteria are gram-negative, catalase-positive, and motile and require oxygen in order to grow and replicate. Pseudomonas and Burkholderia are ubiquitous organisms and a plethora of species has been isolated, mainly from water, soil, animals and plants. Only few species are pathogenic to humans, animals and plants; several species fulfill important ecologic roles.

The most common Pseudomonas species is Pseudomonas aeruginosa (P. aeruginosa). It has been estimated that about 50% of all human beings are asymptomatic carriers of P. aeruginosa, an opportunistic pathogen that may pose a significant threat to immunodeficient people and often causes nosocomial infections. While other Pseudomonas species are also opportunistic pathogens, Burkholderia species may be obligate pathogens and are currently under research as possible arms in biological warfare. Burkholderia species of major interest are Burkholderia cepacia (B. cepacia), Burkholderia mallei (B. mallei) and Burkholderia pseudomallei (B. pseudomallei). Widely distributed resistances to antibiotics complicate PI therapy.

Pseudomonas infection is a condition that may lead to a variety of diseases and that is triggered by bacteria like Pseudomonas aeruginosa (P. aeruginosa), Burkholderia cepacia, Burkholderia mallei and Burkholderia pseudomallei.

Causes
P. aeruginosa is an ubiquitous bacterium that may be encountered in water, soil, on plants, animals and about 50% of the human population. Usually, the presence of P. aeruginosa is not associated with any symptoms. Therefore, P. aeruginosa is not classified as an obligate but rather an opportunistic pathogen. Its opportunity arises when the immune system of the patient is weakened, a situation that may be triggered by conditions such as cystic fibrosis, diabetes mellitus, AIDS or even immunosuppressive therapy in order to treat another illness. Most people contract P. aeruginosa while they are hospitalized to treat one of the aforementioned conditions.

Burkholderia cepacia behaves similarly as P. aeruginosa and is a major concern for people suffering from cystic fibrosis. Burkholderia mallei causes glanders, a disease mainly affecting equids. This disease is eradicated in many countries of the Western world, but may be contracted upon close contact with infected animals in Africa, Middle East and Asia. Burkholderia pseudomallei is not endemic neither in Europe nor North America.

Symptoms
Symptoms highly depend on the organ system that is affected by Pseudomonas infection and may include the following:

• Pneumonia after receiving endotracheal intubation and respiratory support.
• Urinary tract infection after surgical intervention or prolonged use of a catheter. Urinary tract comorbidities may facilitate Pseudomonas infection.
• Otitis externa with ear pain, itching in the external auditory channel and possibly discharge. This disease may progress as malignant otitis externa and trigger cranial nerve palsies and neuronal problems.
• Eye infections.
• Skin infections are most frequently related with stepping on a nail. Deeper structures such as fat, tendons and muscles may also be affected.
• If bacteria enter the blood stream, the infection might spread to other organ systems.

Diagnosis
Samples need to be taken from the infected site in order to culture and identify the causative agent. Also, antibiograms need to be established.

Treatment
Antibiotic therapy is indicated to treat Pseudomonas infection. Only in mild cases, topical antimicrobial treatment will suffice. Usually, systemic therapy is required. The antibiotic will be chosen according to the results of the antibiogram.
Some patients may need to undergo surgery in order to remove damaged tissue and to lower their bacterial load.

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