Pseudomonas aeruginosa: The Alarming Pathogen of Hospital Acquired Infection

Abstract

Pseudomonas aeruginosa is a Gram-negative bacillus that is ubiquitous. It is found in abundant amount in the environment, especially in moist places. Immunocompetent persons get less infected by P. aeruginosa, while immunocompromised patients get more infected by them. The burn patients, patients with cystic fibrosis, and patients who are dependent on any device like ventilator, intravenous catheter, or indwelling bladder catheter are more prone to acquire the infection. It is the main cause of ventilator-associated pneumonia. Patients with neutropenia are more susceptible to P. aeruginosa infections. P. aeruginosa has got several virulence factors through which they can cause disease. They have got attachment factors like Pilli and enzymes. They are one of the main pathogens of healthcare-associated infection (HAI). As P. aeruginosa is multidrug-resistant so this has got an extra contribution to the fact that they can cause HAI more. Common antibiotics like penicillin, carbapenems, cephalosporins, and all other Beta-lactam drugs along with aztreonams and fluroquinolones are resistant to P. aeruginosa. The proper maintenance of hand hygiene and continuous monitoring of hospital devices can lessen the burden of HAI associated with P. aeruginosa infection.

1. Introduction

Nosocomial infections (NI) are a worldwide problem in hospital care. This is an important obstacle that worsens the prognosis of the underlying disease, increases mortality, prolongs hospitalization, worsens the quality of life of patients, and increases the expenses of treatment, so NI needs to be paid special attention [1]. CDC the leading expert of infectious disease control in the United States has set procedures and guidelines that are most widely used worldwide. A nationwide NI surveillance system in the United States has been organized since the 1970s [2].

The United Kingdom also has laboratory service of the British Public Health Service (Public Health Laboratory Service) to monitor the control of healthcare-associated infection (HAI). The main sponsor, which organizes assemblies dedicated to HAI, is the Hospital Infection Society (HIS), that publishes a globally significant and standard journal—the Journal of Hospital Infection [3]. HAIs need to be diagnosed and treated in time, but the most important thing is to maintain proper precaution in various hospital wards, especially in intensive care units (ICU) [4]. Infections developed after hospitalization can lead to remarkable amount of morbidity and mortality, but protective measures can significantly lessen the rate [5]. It is necessary to prevent healthcare individuals to reduce the chances of getting infected and spreading it to other patients and hospital staffs. Thus, the absence of hospital staff from going to work can be reduced, which can improve the quality of the skills of the health providers of ICU. Nosocomial infections are also allied with the burden of extra expenses [6].

Pseudomonas aeruginosa has been detected as a pathogen of hospital patients only in the modern era of intensive treatment and antibiotic resistance. P. aeruginosa causes 10–11% of all NI. It is a Gram-negative, motile, aerobic rod, widely distributed in nature and commonly present in moist environments with simple nutrients in hospitals. P. aeruginosa has comparative resistance to antibiotics and disinfectants which allows it to become established often in very large numbers in fluids, and wet places in hospitals and also to colonize the mucous membranes and skin of patients. In 2017, multidrug-resistant Pseudomonas aeruginosa caused an estimated 32,600 infections among hospitalized patients and 2700 estimated deaths in the United States [7].

2. Compromised host

A compromised host is that individual whose resistance to infection is reduced by disease, therapy, or burns. The host can be compromised by two principal conditions: injured skin or mucous membranes, and a compromised immune system.

The skin, skin appendages, and mucous membranes provide challenging physical barriers in counter to most pathogens. Burn injuries, surgical wounds, trauma (such as accidental wounds), injections, invasive diagnostic procedures, ventilators, intravenous therapy, and urinary catheters can break the first line of defense; thus, making a person more susceptible to disease in a hospital.

Burn patients are especially susceptible to hospital-acquired infections because their skin is no longer an effective physical barrier to microorganisms. Patients requiring invasive procedures usually suffer from serious diseases, which further increases susceptibility to infections. Invasive devices provide a pathway for microorganisms in the environment to enter the body and also help transfer them from one part of the body to another. Pathogens can also proliferate on the devices themselves [4].

It causes disease in humans with abnormal host defenses, especially in patients with neutropenia. In healthy individuals, white blood cells known as T lymphocytes provide resistance to disease by killing pathogens directly, mobilizing phagocytes and other lymphocytes, and B lymphocytes develop into antibody-producing cells to protect against infection. Antibodies neutralize the toxins, inhibit adherence of a pathogen to host cells, and thus kill the pathogens. Drugs, ionizing radiation, steroids, burn injuries, diseases like diabetes, leukemia, kidney disease, mental conditions like stress, and malnutrition can all unpleasantly affect the actions of T lymphocytes and B lymphocytes to compromise the host. Again, HIV affects certain cells which are important for our immune system [8].

It is usually pathogenic when introduced into areas devoid of normal defenses when intravenous or urinary catheters are used. They produce systemic diseases with the help of pilus, enzymes, glycocalyx, and toxins.

Pseudomonas aeruginosa has large intrinsic resistance to multiple antibiotics. This characteristic and its quick ability to acquire new antimicrobial resistance make this pathogen a growing problem in infectious disease pathology, especially when nosocomial in origin. Traditionally P. aeruginosa is not treated with single-drug therapy because the success rate is very low and the bacteria can rapidly develop resistance when a single drug is used. Multidrug resistance has become a major issue in the management of hospital-acquired urinary tract infections [7].

3. Antigenic structure and toxins

Pseudomonas aeruginosa specifically produces a variety of virulence factors including adhesins, enzymes, and toxins. Pili extends from the cell surface and help in attachment with host epithelial cells. Lipopolysaccharide, an element of the cell wall structure is responsible for many of the endotoxic properties of the organism. Most of the Pseudomonas aeruginosa isolates from clinical infections produce extracellular enzymes, including elastases, proteases, and two hemolysins- a heat-labile phospholipase C and a heat-stable glycolipid. A pigment known as pyocyanin produced by P. aeruginosa is responsible for the production of hydrogen peroxide and superoxide and stimulates IL-8. The increased release of IL-8 serves as an attractant for neutrophils. The other pigment pyoverdine is a siderophore; it binds to iron.

Pseudomonas aeruginosa produces exotoxin A which causes tissue necrosis and is lethal for animals when injected in purified form. The toxin blocks protein synthesis. P. aeruginosa produces four type III secreted toxins; exoenzyme S, exoenzyme T, exoenzyme U, and exoenzyme Y. Among these, exoenzymes S and exoenzyme T are enzymes with GTPase and ADP-ribosyl transferase activity whereas Exoenzyme U is a phospholipase and Exoenzyme Y is an adenylyl cyclase [9]. These toxins cause cell death or inhibit the host’s response to infection.

4. Clinical diseases

4.1 Pulmonary infection

Pseudomonas aeruginosa causes infection of the lower respiratory tract that can differ in severity from asymptomatic colonization or benign inflammation of the bronchioles to severe necrotizing bronchopneumonia. Colonization can be seen in patients with cystic fibrosis, other chronic lung diseases, and patients who have neutropenia. Infections in patients with cystic fibrosis have been connected with exacerbation of the underlying disease and invasive pulmonary disease. Mucoid strains are associated with these strains and are difficult to remove because chronic infections with these bacteria are associated with a progressive increase in antibiotic resistance.

Nosocomial pneumonia is the second most common nosocomial infection in pediatric ICUs after intravenous catheter infections of the bloodstream. It can occur in any patient but is most common in infants, young children, and patients over 65 years of age which means they are immunocompromised. Patients in pediatric ICUs who are most at risk for pneumonia are patients who have been intubated and are under mechanical ventilation. The risk intensifies as vocal cords remain open and there is an increased risk of aspiration of gastrointestinal contents. The chances of developing nosocomial pneumonia are 6–20 times higher in patients who undergo mechanical ventilation rather than those who do not need that. Ventilator-associated pneumonia (VAP) is defined as a lung infection resulting in pneumonia that occurs in people who are on mechanical ventilation for at least 48 hours.

Factors that can initiate the development of VAP in children are immunodeficiency, immunosuppression, and neuromuscular blockade. The other factors are myasthenia gravis, burn injuries, administration of steroids, and hyperalimentation. Children who are at higher risk of VAP are those with antibiotics, with a prolonged stay in the ICU, with intravenous channels who have greater risk of hematogenous spread, H2-receptor blocker intake, reinsertion of endotracheal tube, and transport of patient outside during intubation as they may get contaminated by the environment. The presence of a nasogastric tube provides a direct pathway from the upper gastrointestinal tract to the oropharynx.

The risk of nosocomial pneumonia will be increased by the use of nebulizers and manipulation of the ventilator circuit. VAP in children accounts for 10–26% of nosocomial infections. Nosocomial pneumonia accounts for a 20–70% mortality rate which is highest in all pediatric nosocomial infections, although the period of endotracheal intubation increases the risk of nosocomial pneumonia, which is highest during the first 2 weeks of intubation.

Within 5 days almost all the children who have received endotracheal tube gets colonized by nosocomial microorganisms. The most commonly identified bacteria are gram-negative bacilli, especially P. aeruginosa, in which mortality is higher. One of the leading causes of ventilator-associated pneumonia (VAP) in the United States and Europe [10] is P. aeruginosa, which poses unique challenges for its clinical management and increase in incidence.

4.2 Urinary tract infections

Nosocomial infection accounts for 20–49% in all the cases of urinary tract infection, out of which 10% is contributed by Pseudomonas aeruginosa which usually occurs after catheterization, instrumentation of the urinary system or surgery, resulting in discomfort, pyelonephritis, morbidity, and in some cases, it may lead to death. Insertion of catheter can disrupt the mucosal lining which may lead to easy entry of pathogens into the urinary tract causing bacterial colonization [11].

In UTI Pseudomonas aeruginosa is a key uropathogen with high prevalence in reported cases worldwide [12].

4.3 Skin and soft tissue infection

P. aeruginosa can cause a variety of primary skin infections and the most recognized among them is the burn wound. Colonization of a burn wound followed by localized vascular damage, tissue necrosis, and ultimately bacteremia. The moist surface of the burns and the inability of neutrophils to enter the wound predispose the patients to such infections.

Picture showing the typical greenish pus of Pseudomonas aeruginosa in a patient with surgical wound infection.

4.4 Bacteremia

Bacteremia may also occur due to P. aeruginosa which is a cause of high mortality rate. Bacteremia occurs most often in patients with neutropenia, diabetes mellitus, extensive burns, and malignancies. In most cases, they originate from the lower respiratory tract, urinary tract, and skin and soft tissue infections [13].

4.5 Antimicrobial resistance of Pseudomonas aeruginosa

Antimicrobial resistance happens when germs like bacteria and fungi gain the ability to resist the action of an antimicrobial agent that was designed to kill them, to which it was previously susceptible [14]. HAI caused by antibiotic-resistant P. aeruginosa has appeared as an alarming concern in health care settings as day-by-day MDR strains (i.e., resistance to at least three antibiotics) are increasing. P. aeruginosa shows resistance to various antimicrobial agents because of its outer membrane with low permeability. Although some other mechanisms are also responsible for their intrinsic resistance including, the efflux system which expels antibiotics out of the bacterial cell, and the production of the antibiotic-inactivating enzyme.

This microorganism is capable of adopting to its environment due to diversity in its structure and functioning. When exposed to antibiotics the bacteria survive by developing antibiotic resistance through various mechanical and chemical processes, giving it a lead against the antibiotics acting on it. The development of antibiotic resistance has been testified at some point of host colonization of CF patients, wherein P. aeruginosa strains increase and accumulate resistance for the duration of antimicrobial therapy. Research has suggested a robust association between multiple usages of ciprofloxacin with the accelerated incidence of ciprofloxacin-resistant strains. Therefore, some other element connected with the growth of MDR P. aeruginosa is related to the frequent use of antimicrobial agents. The development of this resistance can be a result of the consequence of a mutational instance or purchase of resistance gene through direct gene transfer which may rise at some point during antibiotic therapy, mutational events may lead to overexpression of endogenous beta-lactamases or efflux pump, and expression of specific porins.

Bacterial cell wall peptidoglycan synthesis is inhibited by Beta-lactam antibiotics. This group of drugs like penicillin, cephalosporin, carbapenem, and monobactam are usually effective against P. aeruginosa. Among these drugs, piperacillin and ticarcillin (penicillins), ceftazidime (third-generation cephalosporin), cefepime (fourth-generation cephalosporin), aztreonam (monobactam), imipenem, meropenem, and doripenem (carbapenems) are efficacious beta-lactam that is frequently used in of Pseudomonas aeruginosa treatment. B-lactamase enzymes work as key factors in developing resistance to B-lactam antibiotics. These develop resistance by breaking the amide bond of the B-lactam ring which results in demolishing the effect of the antibiotic therapy. The action of the drug is countered either by the expression of endogenous B-lactamases or by the expression of acquired beta-lactamases. Characterized by their substrate specificity hundreds of B-lactamases have been identified so far. Amber’s molecular classification has put forward four major classes of B-lactamases found in P. aeruginosa: A-D. Classes A, C, and D catalyze the serine residue which inactivates the B-lactams whereas class B or Metallo-B-lactamases (MBLs) utilizes zinc.

P. aeruginosa is evidently vulnerable to carboxypenicillins, ceftazidime, and aztreonam however it could attain resistance through mutation in a gene that may result in hyper-manufacturing of AmpC beta-lactamase.

P. aeruginosa produces an inducible chromosome encoded AmpC beta-lactamase (cephalosporins) that belongs to molecular class C, based totally on Ambler and the first functional institution. Usually, the enzyme is produced in low quantities (‘low-level’ expression) and determines resistance to aminopenicillins and most of the early cephalosporins.

Fluoroquinolones develop resistance when mutation occurs within the gene encoding for DNA gyrase or topoisomerase or by active transport of drug out of the cell. Mutation of topoisomerase may occur in gyrA/gyrB genes at the active site of the enzyme, which is the determinative region motif for quinolone-resistance. This leads towards altered amino acid sequences of the A and B subunit, and hereafter a modified topoisomerase II with low binding affinity to quinolone molecules are formed. Alterations of topoisomerase IV occur as a result of point mutations in ParC and ParE genes encoding ParC and ParE enzyme subunits, individually. Another mode for fluoroquinolone resistance involves the overexpression of efflux [13].

4.6 How can we prevent infection?

Patients and care providers have to:

Preserve their palms so that they do not get contaminated and also do not spread germs that can cause infection.

Clean hands with soap and water or use a hand sanitizer containing alcohol prior to touching any wounds or handling any medical device.

Remind healthcare providers and caregivers to clean their palms before touching the patient or dealing with scientific devices.

Allow healthcare group of workers to clean their room daily whilst in a healthcare place.

Healthcare vendors need to be careful to suggest contamination control, which includes hand and environmental hygiene (e.g., cleansing of affected patient rooms and shared devices) to reduce the chance of spreading those germs to other patients.

Healthcare centers need to have appropriate water control plans that help ensure water quality and reduce the risk of exposure to potentially harmful germs like P. aeruginosa [6].

5. Conclusion

Healthcare-associated infections are worth preventing in terms of benefits in morbidity, mortality, duration of hospital stays, and cost. Educational interventions promoting good hygiene and aseptic techniques have a great effect on the control. Constant vigilance and attention by healthcare providers can be efficient to maintain their personal hygiene and the devices associated with the treatment, which contributes to lessening the occurrence of HAI.