Literature Review
MAALRAWAILI
Clinicalimpactofacinetobacternosocomialinfectionsinhospitals1.docxClinical Impact of Acinetobacter Nosocomial Infections in Hospitals
Nosocomial infections, interchangeably known as hospital-acquired infections, have become a major concern following the emergence of the Acinetobacter spp. that has infected up to 10% of the hospital patients. Globally it has affected over 2 million people with a mortality rate of around 90,000 per year (Al-Gethamy et al., 2017). Acinetobacter is the most common causative agent of nosocomial infections in clinically ill patients. These opportunistic bacteria are gram-negative, among which the Acinetobacter baumannii strain is the most significant due to high mortality, multidrug resistance, and treatment expenses (Ayobami et al., 2019). The size of the Acinetobacter spp. ranges between 1.0–1.5 μm by 1.5–2.5 μm in during the growth phase. In the stationary phase, the pathogen develops into a coccoid structure, arranged in the form of long chains of different lengths (Jung et al, 2015). The species of the Acinetobacter genus are non-motile, indole-negative, strictly aerobic, citrate positive, catalase-positive, oxidase-negative, and Gram-negative.
According to a study conducted in hospitals of Turkey, 16.6% of nosocomial infections were caused by A. baumannii. The majority of these patients constituting 68.9% were from the ICU while 52.5% were patients with respiratory tract infections (Dizbay et al., 2010). Known to cause severe illness, the bacteria mostly infects people with weak immune systems, leading to an increase in mortality rate (Lin et al., 2011). On the human body, the pathogen populates the skin, digestive tract and the oropharynx of the hospitalized patients (Jung et al 2015). (Seifert et al., 1997) conducted a study in which the Acinetobacter spp. isolates were identified from different regions such as hand, nose, throat, forehead, ear, conjunctiva, and trachea of a healthy individual.
The apparent treatment for the infection would be antimicrobial drugs but due to the development of resistance over the years, hospital-acquired infections have become difficult to treat, thus worsening the illness (Al-Gethamy et al., 2017).
This review reflects on the clinical impact of the Acinetobacter spp., especially the A. baumannii strain in particular, which is the most common cause of nosocomial infections in the hospitals.
1. Epidemiology
Substantially, A. baumannii is a health maintenance linked pathogen which is the source of the epidemic hospital-acquired diseases such as septicemia, bacteremia, ventilator-associated pneumonia, wound sepsis, endocarditis, meningitis, and urinary tract infections (Vashist et al., 2011). Multidrug-resistant (MDR) Acinetobacter constitutes a negligible menace in the health of medical professionals or their families. This is because MDR Acinetobacter infrequently gives rise to any consequential disease in an immunologically well person. Infectious breakouts usually occur in mechanically ventilated patients admitted in intensive-care and burn units (Kanafani et al, 2014).
1.1. Global Epidemiology of A. baumannii
1.2. Middle East Epidemiology of A. baumannii
Despite their decent healthcare system, middle eastern countries such as Saudi Arabia, Bahrain, UAE, and Lebanon have reported cases of MDR A.baumannii infections in the hospitals (Almasaudi, 2018). A study was conducted in the ICU of Riyadh Military Hospital, Saudi Arabia to assess the prevalence of MDR strain infections. The results depicted that 40.9% of the test samples were infected by A. baumannii. In another study, among the ventilator-associated pneumonia patients, 26.5% of them were infected by Acinetobacter spp. between the years 2005 and 2009. From the year 2006 to 2015, the prevalence of the resistant strain of the bacteria rose from 19% to 92.1%.
In 2015, researches showed that Acinetobacter spp. is highly resistant to antibiotics. The rate of resistance rose from 55% in 2010 to 67% in 2013. The increasing resistance was a concern especially in the Makkah region, which hosts the largest number of people annually from all over the world, threatened with a high risk of transmission of the infectious disease (Kharaba et al., 2019).
The bacteria colonize the respiratory tract, oral cavity, intestinal cavity, and skin. A. baumannii has been found to be able to survive in harsh conditions such as limited nutrient supply and low water content. With their ability to subsist on dry surfaces, transmission in the medical environment from surface to surface is enabled. It has been experimentally proved that A. baumannii has a higher survival rate on dry surfaces than Escherichia coli, lasting over 4 months. Later researches depict that the Acinetobacter spp. are able to survive in both dry as well as wet conditions. With these beneficial characteristics, the bacteria are able to thrive and disseminate in the hospital environment infecting patients, especially immune-compromised patients. Moreover, Acinetobacter spp. have been more frequently found on the hands of hospital staff, particularly of the ICU, and inanimate objects as compared to the S. aureus and Pseudomonas spp. (Kanafani et al, 2014; Lee et al., 2011).
The Acinetobacter spp. causes infections which include, bloodstream infections, nosocomial pneumonia, urinary tract infections, wound infections, and skin and soft tissue infections. The highest rate of infection has been observed in summers which confirms that the bacteria thrive and multiplies in humidity and elevated temperatures. (Al-Gethamy et al., 2017) led a hospital-based experiment to determine the risk factors associated with MDR A. baumannii in patients admitted in Al Noor Specialist Hospital between January and August. Figure 1 illustrates the most frequent sites where the bacteria colonizes and develops disease. The highest number of cases were of hospital acquired pneumonia mounting up to 77.3% of the total patients.
Percentage
Figure 1: Acinetobacter baumannii sites of infection in hospital acquired infections in Saudi Arabia (Al-Gethamy et al., 2017)
Since one of the locations where the bacteria colonizes in the human body is the respiratory tract, a larger percentage (47.9%) of the patients infected by the pathogen exhibit symptoms of pneumonia (Gaynes et al, 2005). According to the National Nosocomial Infection Surveillance System (NNIS), the USA records 10% of the ICUacquired pneumonia infected by A. baumannii; while ICUs in Europe record 21.8% of infections. The increase in numbers has led to an increase in the mortality rate, reaching up to 40% (Wisplinghoff et al., 2000).
Among the major causes of hospital-acquired bloodstream infections, A.baumannii is ranked 10th with being the most frequent infection-causing agent in the USA, accounting for 1.3% of them and the mortality rate being a whopping 58% (Wisplinghoff et al., 2000).
3.3. Community-Acquired Infections
Acinetobacter has the ability to easily reside in the tracheostomy sites which leads to community-acquired tracheobronchitis and bronchiolitis in immuno-compromised adults and healthy children. While it is uncommon for it to cause community-acquired pneumonia and sepsis, A. baumannii has been identified in some regions of Asia and Australia in the monsoon seasons, in people with chronic obstructive pulmonary disease or who have a history of alcohol abuse (Peleg et al., 2008).
3.4. Urinary Tract Infection
A. baumannii is a rare cause of urinary tract infection; a study observes that only 1.6% of the patients were suffering from ICU-acquired UTIs. Since this pathogen relates to catheter-associated colonization or infection, it is uncommon for it to be a cause of intricate UTI in outpatients (Peleg et al., 2008).
3.5. Meningitis
Another disease caused due to the MDR property of the A. baumannii is the post neurosurgical nosocomial meningitis. Tests confirm that Acinetobacter accounts for 10% of Gram-negative bacillary in adults suffering with acute bacterial meningitis. This has resulted in hiked up mortality rate, which is up to 70% (Peleg et al., 2008).
3.6. Other infections
While not significant, some rare cases of endocarditis caused by A. baumannii also exist majority of them involving prosthetic valves. Other infections that A. baumannii may cause are peritonitis, endocarditis, keratitis or ophthalmitis which involves the usage of contact lens use or followed by eye surgery (Peleg et al., 2008).
4. Modes of Transmission
Invasive medical procedures following poor hygienic conditions and practice is a major reason for the transmission of Acinetobacter nosocomial infections. An immunodeficient individual has increased chances of contracting the infection. Furthermore, hospital staff, who are associated with various units, serve as carriers, and disseminate the pathogens (Almasaudi, 2018). There are multiple modes of transmission, discussed as follows;
4.1. Hospital Environmental Contamination
Inanimate objects and medical equipment that come in the vicinity of the patients could serve as a reservoir or fomites for Acinetobacter pathogens. These include bed rails, bed linens, pillows, curtains, tables, door handles, and sinks in addition to cleaning equipment. The most frequently identified source for outbreaks has been the contamination of the medical equipment, most common reports referring to the respiratory equipment.
4.2. Air-Borne Transmission and Aerial Dissemination
While not much was known about the airborne transmission of the infection, studies conducted by (Weernink et al., 1995) claim that the Acinetobacter spp. are able to disperse from feather pillows. Another research was conducted by (Houang et al., 2001), proving that the aerial dissemination of Acinetobacter pathogens is likely.
4.3. Hands of Healthcare Personnel
The medical staff is most likely to be the vectors of A. baumannii, which colonizes on the hands of the hospital staff. Associating with patients of various units, the healthcare personnel facilitate the dissemination of the outbreak strains. Epidemiological studies suggest the rate at which the hands of the physicians and nurses carry the pathogens were found to be varying over 3% and below 23%, albeit temporary, unless the skin is damaged.
Figure 2: Transmission pattern of A. baumannii in a hospital environment (Lee et al., 2011)
Since first discovered, A. baumannii has developed resistance to the antibiotic drugs over the 40 years, giving rise to the multidrug resistance (MDR) strains of the pathogen. The prevalence of the MDR strains have become a concern all around the world and is now being recognized as the foremost nosocomial infection causing agent. By the year 2010, A. baumannii MDR strain had become the causative agent for half of the nosocomial infections in the USA (Pogue, Mann, Barber, & Kaye, 2013). MDR strain outbreaks will not only affect mortality and morbidity but will also cause a huge dent in the healthcare system’s economy. The Acinetobacter spp. have a noteworthy capability of acquiring the foreign genetic material, classifying them as “naturally transformable”, leading to enhanced antibiotic resistance. Gene transfer among A. baumannii takes place through conjugation, mobile genetic elements, transformation, and transduction. Research conducted in1969 by Juni and Janik lead to the discovery of a novel strain which is hyper transformable and has the ability to take up and recombine the genetic material from lysed bacteria, into its own genome. This newly found strain was named A. calcoaceticus.
The classifications of the mechanisms of antibiotic resistance in A. baumannii are based on variations in Penicillin-binding proteins (PBPs), modifications in OMP3, antimicrobial-inactivating enzymes, and efflux pumps. A. baumannii strains that are resistant to aminoglycosides are equipped with genes that code for aminoglycoside-modifying enzymes. Quinolones resistance is due to mutation that causes modification in the DNA topoisomerase IV or gyrase structure in the quinolone’s resistance-determining regions of the parC and gyrA genes. The mutation results in the reduction of the binding affinity of quinolones to the enzyme-DNA complex.
The mechanism of resistance to quinolones by efflux systems reduces the intracellular accumulation of drugs. Carbapenem resistance occurs by means of hydrolysis which sequentially is instigated by acquired and intrinsic carbapenem-hydrolyzing β-lactamases (carbapenemases). The tetracycline resistance mechanism is classified into two: Transposon-mediated efflux pumps TetA and TetB play their roles in the tetracycline efflux and control of both minocycline and tetracycline efflux respectively. The former comprises the occurrence of ribosomal protection protein-encoded by the gene Tet(M), which is responsible for shielding the ribosome from tetracycline, minocycline, and doxycycline (Kharaba et al., 2019).
The Infectious Diseases Society of America recognizes A. baumannii as a significant threat, labeling it as “red alert” pathogen. While the increased resistance has rendered most antimicrobials ineffective, a few remain reliably effective in handling the Acinetobacter nosocomial infections. Nevertheless, the pursuit of new drugs is still ongoing while the older ones are being reevaluated.
6.1. Carbapenems
Increasing resistance to carbapenems, also known as imipenem or meropenem, has been observed resulting in concerns arising in the treatment of the Acinetobacter MDR strains infection. However, in cases where the Acinetobacter isolates are still prone to it, carbapenems are continuing to be used.
6.2. Sulbactam
Studies demonstrate that the bactericidal activity of Acinetobacter spp. impedes when Sulbactam is used, which inhibits the β-lactamase (resistance providing enzymes). A healing rate of up to 67% has been observed in treating infections caused by MDR A. baumannii, which include pneumonia, meningitis, urinary tract infections, and peritonitis (Almasaudi, 2018).
6.3. Aminoglycosides
Aminoglycosides such as Amikacin and Tobramycin have been opted as therapeutic agents against MDR A. baumannii that are yet susceptible to the antimicrobial class. Albeit, these drugs are used not alone but in combination with other active agents. Resistance to amikacin and tobramycin are correlated with efflux pump or aminoglycoside-modifying enzyme mechanisms (Almasaudi, 2018).
6.4. Colistin
Colistin is a cationic protein which belongs to the family polymyxin. Although its potential was mostly exploited in 1960s and 1970s, it was not prescribed due to resultant side effects i.e. neurotoxicity and nephrotoxicity. This family of drugs is now being used against the resistant strain of the pathogen. Colistin as an anti-microbial agent has proved to be highly effective with success rate of 57%-77% curing patients with symptoms of pneumonia, sepsis, bacteremia, central nervous system and intra-abdominal infections (Vourli et al., 2015).
6.6. Tigecycline
Tigecycline derives from the minocycline and exhibits bacteriostatic activity against MDR A. baumannii (Dinc et al., 2015). Some MDR isolates have shown signs of high level of resistance to tigecycline, brining out the concerns of ineffective antimicrobial mediated efflux pumps.
Figure 3: Antibiotic test results illustrating susceptibility of A. baumannii to different antimicrobial agents
Figure 3 demonstrates the effectiveness of different drugs against A. baumannii. 92% of the pathogen were prone to the antibiotics Ciproflaxin and Ceftazidime, followed by trimethoprim with 83% and amikacin with 79% effectiveness (Al-Gethamy et al., 2017).
7. Conclusion
Acinetobacter has been recognized as a problematic pathogen becoming a major causative agent of nosocomial infection with widespread cases. Moreover, the increasing number of cases is not the only problem, but the emerging multi-resistant strains have brought out the concerns with only a few antimicrobial agents being effective against it. This review study focuses on the clinical impact of the Acinetobacter nosocomial infections in the middle eastern countries such as Saudi Arabia and globally. In light of this, strict control measures must be implemented in order to control the dissemination of the pathogens in the medical environment. Furthermore, improved sanitation procedures and hygiene of the healthcare personnel may contribute to the control of the spread of the bacteria.
8. References
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