Background

Pseudomonas is an aerobic, gram-negative bacterium of low virulence, was discovered by Gessard in 1882. This organism is reported to live in water and soil and is mostly found where there is moisture. Pseudomonas species can be isolated from soil, water, plants, animals and more than 50% of humans are colonized by P. aeruginosa, which is the most common. 

Pseudomonas is an opportunist pathogen that commonly is involved in hospital-acquired infections. It can result in very dangerous and even lethal diseases and is characterized by a high level of pathogen’s resistance to antibiotics – new forms of resistance may appear as soon as antibiotics hit the pathogen. Certain species associated with old diseases are now being looked at in terms of biological warfare. 

The organisms of this genus are divided into five groups according to the homology of the rRNA/DNA. Among the more than 20 species found in human clinical specimens, four notable ones are: 

P.aeruginosa which belongs to homology group I 

Burkholderia (Pseudomonas) cepacia (group II). 

Burkholderia (Pseudomonas) pseudomallei (group II). 

It belongs to group II; Burkholderia (Pseudomonas) mallei 

Epidemiology

P.aeruginosa is a major cause of many hospital-acquired infections in the U. S., including pneumonia in ICU patients, osteochondritis and UTIs. It contributes to 10% of hospital-acquired infections and is prevalent in external otitis and corneal ulcer diseases. Globally, Burkholderia cepacia is more dangerous to cystic fibrosis patients as its infection to the lung leads to high mortality rates. 

Pseudomonal infections patients mostly presents with bacteremia pneumonia and sepsis, and the mortalities associated with P. aeruginosa bacteremia are often above 50%. In terms of demographic differences, Black men, young men who are IV drug users, and infants are most vulnerable to specific pseudomonal infections: pseudomonal pneumonia is most often observed in adults with cystic fibrosis. 

Anatomy

Pathophysiology

Pseudomonas aeruginosa is a gram-negative bacterium that normally does not produce any disease in the healthy hosts but is a significant pathogen in immunocompromised patients or mechanically wounded ones, including the patients with burns, cystic fibrosis or with catheters. The bacterium’s pathogenesis involves various toxins and the ability to invade and spread throughout the body in three stages: adherence and invasion, primary and secondary infection, and hematogenous spread. It is also attributed for its antibiotic resistance and researchers are currently working on efflux pump inhibitors as treatment. 

Burkholderia cepacia (previously classified under Pseudomonas cepacia) was isolated from plants before it was associated with human diseases, especially among cystic fibrosis patients suffering from pneumonia and septicaemia. It has also been associated with catheter-related infections and was in the past reported to affect soldiers by causing foot infections. 

Burkholderia mallei (earlier classified as Pseudomonas mallei) is a bacterium that causes glanders, a contagious Diseases affecting animal mostly horses occasionally affecting humans mainly through direct contact with the affected animal. The disease may vary from skin infections, abscesses, and soft tissue to septicemia furnishing so called blood poisoning. 

Burkholderia pseudomallei (formerly Pseudomonas pseudomallei) is the causative agent of melioidosis, which is to glanders but differs about its epidemiology. This type is usually discovered in water and soil that contains filth and then spreads to humans and animals through contact. This may manifest as simple abscesses to overwhelming septicemia. The pathophysiology is related to the fact that bacteria can divide rapidly within a few hours. 

Etiology

Compromised Barriers: Aqueducts for bacterial invasion include burn injuries, IV lines, catheters, or surgical wounds. 

Immunocompromised States: Risk factors include chronic diseases such as cystic fibrosis, AIDS, neutropenia, and immunosuppressive treatments in patients. 

Virulence Factors: P. aeruginosa employs toxins, proteases, biofilm, and efflux pumps to enter, avoid eradication, and disseminate to various tissues of the host. 

Stages of Infection: Infections occur by bacterial attachment, local invasions, and spread of bacteria systemically that may cause severe diseases such as sepsis. 

Genetics

Prognostic Factors

Immune Status: HIV/AIDS patients, patients with neutropenia or those on immunosuppressive drugs have a poor prognosis. 

Site of Infection: Conditions such as bacteremia pneumonia, sepsis and meningitis are conditions observed to lead to high mortality. 

Antibiotic Resistance: Infections with the multidrug-resistant strain of Pseudomonas have had poor prognosis mainly because of the many limitations as regards the management of such infections. 

Patient Age: These patients fare worse than the others because their systems can barely put up a fight to boot out thrown out pathogens. 

Presence of Comorbidities: Co-morbidities such as cystic fibrosis or diabetes are often known to aggravate the condition and its outcome. 

Clinical History

Age Group 

• Children: Pseudomonas infections occur most frequently in hospitals among children; in children with cystic fibrosis and those with burn injuries most often. Respiratory infection, otitis externa and, skin infection are basic challenges that are often experienced. 
• Adults: Usually observed in adults with certain chronic conditions like diabetes, chronic lung disease, or weaker immune system through immunosuppressive therapy. Multiplying complications, UTIs, respiratory infections, and bacteremia also remain common. 

Physical Examination

Skin: Infections may also cause green or blue-coloured pus or discharge, commonly in a wound infection. Patients may find necrotic tissue or have a grape-like smell that indicates the presence of a severe infection. 

Respiratory: With pneumonia look for features indicative of respiratory distress which could be wheeze, crackles or reduced breath sounds. The patient may have a productive cough with severe, thick, purulent sputum that is usually green in color. 

Urinary Tract: These may include dysuria, slow stream, urgency and frequency, and even suprapubic or flank pain or tenderness. 

Ear (Otitis externa): Earache associated with redness and swelling of the ear canal with or without discharge and ear painful on movement. 

Age group

Associated comorbidity

• Cystic fibrosis 
• Diabetes 
• Chronic obstructive pulmonary disorder 
• Immunosuppression 
• Burns 

Associated activity

Acuity of presentation

Mild to Moderate: Otitis externa, minor urinary tract infections and limited skin infections do not display the severe symptoms as those mentioned above and can therefore be treated as outpatients. 

Severe: For respiratory infections especially in the cases of cystic fibrosis or in patients on mechanical ventilation and bacteremia the illness may be acute severe and necessitate admission and intensive care. 

Differential Diagnoses

• Bronchiectasis Imaging 
• Diarrhea 
• Emergent Management of Acute Otitis Media 
• Empyema Imaging 
• Fever Without a Focus 
• Bacteremia 
• Chemical Burns 
• Electrical Injuries in Emergency Medicine 
• Emergent Management of Thermal Burns 
• Fever in the Infant and Toddler 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Antibiotic Therapy: 

Serious infections: Co-infection with piperacillin-tazobactam, cefepime and carbapenems along with aminoglycosides is another combination regime.  

Less severe infections: These include oral preparations such as ciprofloxacin or levofloxacin. 

Supportive Care: Ensure hydration and nutrition. Managing wounds with cleaning and debridement procedures. 

Source Control: Abscesses involving the anatomic drain and infected cavitation. They should either be removed or, if present, replaced. 

Monitoring and Follow-Up: Patient response toward medication and therapy should be evaluated often and further modification should be made. Control for toxicity and make sure the patient’s level is therapeutic. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

use-of-a-non-pharmacological-approach-for-treating-pseudomonas-infections

Wound dressing is important and essential practices include daily cleaning whereby any dead or infected tissue is removed to prevent worsening of the infection and increase bacterial load. It is also necessary to clean the wounds with antiseptics or saline to minimize chances of introducing additional pathogens into the wound. 

In certain cases, patients might require surgery for appropriate management of the infection for instance, drainage of Abscesses or excision of infected tissues. 

Measures such as washing of hands or use of gloves and other barriers are among the measures mostly advised when it comes to the management of the infection. The main activities that we should do frequently are the washing of hands and the use of the hand sanitizers.  

Supplementary support is also required and the same applies to nutritional support. A healthy diet helps to prevent illnesses, and the immune system, if necessary, some vitamins may be prescribed. 

Role of Antibiotics in the treatment of Pseudomonas-infections

Ceftazidime: This third-generation cephalosporin is the drug of choice in treating Pseudomonas infections of the central nervous system and melioidosis. It exhibits potency against both Gram positive and negative organisms and has a higher efficacy against resistant strains but comparatively less effective against Gram positive organisms. It works by binding with one or more specific proteins, namely the penicillin-binding proteins that disallow the bacterial development. 

Cefepime: This is a fourth-generation cephalosporin which is indicated for central nervous system infections along with Ceftazidime. It is effective against gram-negative organisms and enhances the gram-positive activity of the third generation cephalosporins. 

Meropenam: This is a carbapenem antibiotic that work via the inhibition of the cell wall synthesis, this antibiotic is active against most of the gram-positive and gram-negative bacteria. Meropenem has increased activity against gram-negative bacteria compared to imipenem while it appears to be slightly less effective against Staphylococci and Streptococci. 

Imipenem and Cilastatin: This combination is for the infections due to more than one pathogen when other antibiotics do not have adequate coverage or their use may cause toxicity. It can slow down the metabolism of imipenem hence helping in prolonging the effectiveness of the drug. 

Piperacillin and Tazobactam: This penicillin namely Pseudomonas is taken with beta-lactamase inhibitor and work during bacterial replication by inhibiting cell wall synthesis. It is active against most gram positive, gram negative and anaerobic organisms. 

Ticarcillin and Clavulanate: As with the piperacillin tazobactam, this is also an antipseudomonal penicillin with a beta-lactamase inhibitor. Though its actions include limiting cell wall synthesis during bacterial growth, it is broad-spectrum activity against gram-positive, gram-negative and anaerobic organisms. 

Tobramycin: This is aminoglycoside used for skin, bone, and structure skin infections caused by Pseudomonas aeruginosa, Staphylococcus aureus, Proteus species, Escherichia coli, Klebsiella, and Enterobacter. 

Gentamicin: Another aminoglycoside instrument gentamicin which brokers against gram-negative bacteria and may be utilised in combination with antibiotics operational against gram-positive microorganisms and anaerobes. It is not the preferred drug of choice, but it is used in cases where other antibiotics could cause adverse side-effects or in cases of mixed infections. 

Ciprofloxacin: This fluoroquinolone active against Pseudomonas; some Streptococcus; MRSA; Staphylococcus epidermidis; almost all gram-negative organisms does not active against anaerobes. It prevents DNA synthesis and is used widely in adult’s urinary tract infection due to Pseudomonas and some skins infection. 

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Surgical Debridement: It also involves wound debridement where dead tissues that harbor bacteria are cleared in a bid to minimize bacterial count and facilitate faster healing. Surgery which includes removal of damaged tissue usually takes place in a new environment to eliminate further infections. This is particularly important in chronic or severe infections because the effectiveness of an antibiotic depends on the type of infection and the severity. 

Abscess Drainage: This may be done by simple needle aspiration or by an incision and drainage if the abscess has become large and surgically accessible. Drainage ensures that the antibiotics get to the parts of the body that is infected, within the shortest time possible. 

Removal or Replacement of Indwelling Devices: It requires the deactivation or elimination of some tools that may be infected or contaminated with the virus. For example, if the central line or urinary catheter is likely to be infected; it can be removed and replaced to suppress the infection. 

Hyperbaric Oxygen Therapy (HBOT): The patient inhales oxygen in a high-pressure chamber, which increases the necessary oxygen to the tissues of the body and promotes auto healing. This is usually recommended for cases where the infection is long standing or extensive. 

use-of-phases-in-managing-pseudomonas-infections

Managing Pseudomonas infections typically involves a phased approach: First, identify and evaluate the patient through clinical examination and laboratory investigations. Subsequently, start empirical antibiotic therapy using agents with wide antibacterial spectrums and give supportive treatment. Upon availability of culture and sensitivity outcomes, they can make necessary changes to target the therapy nicely that would combat the infection. Follow up the patient’s condition and do other cultures to make sure any adverse effects are resolved. Discuss any issues, including antibiotics, treatment with antibiotics, need for an operation or other procedures. Follow infection control measures and advise the patient on practice, signs, and measures you should take to avoid the spread of the infection. In chronic cases, assess for cause and think long-term management, check for other conditions. 

Medication

Future Trends

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References

Pseudomonas aeruginosa – StatPearls – NCBI Bookshelf (nih.gov)