Ainetobacter Baumannii
Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul
Baumann. It can be an opportunistic pathogen in humans, affecting people with compromised immune
systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples (leading to the common misconception that A.
baumannii is a soil organism, too), it is almost exclusively isolated from
hospital environments. Although occasionally it has been found in
environmental soil and water samples, its natural habitat is still not known.
Bacteria of this
genus lack flagella, whip-like structures many bacteria use for locomotion,
but exhibit twitching or swarming motility. This may be due to the activity
of type IV pili, pole-like structures that can be extended and
retracted. Motility in A. baumannii may also be due to the excretion
of exopolysaccharide, creating a film of high-molecular-weight sugar chains behind the bacterium to move
A. baumannii is part of the ACB complex (A.
baumannii, A. calcoaceticus, and Acinetobacter genomic species
13TU). It is difficult to determine the specific species of members of the ACB
complex and they comprise the most clinically relevant members of the
genus. A. baumannii has also been identified as an ESKAPE pathogen (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), a group of pathogens with a high rate
of antibiotic resistance that are responsible for the majority of nosocomial
infections.
Colloquially, A. baumannii is referred to as
"Iraqibacter" due to its seemingly sudden emergence in
military treatment facilities during the Iraq War. It has continued to be an issue for veterans and
soldiers who served in Iraq and Afghanistan. Multidrug-resistant A.
baumannii has spread to civilian hospitals in part due to the transport of
infected soldiers through multiple medical facilities. During the COVID-19
pandemic, coinfection with A. baumannii secondary to SARS-CoV-2
infections has been reported multiple times in medical publications.
Omp A
Adhesion can be a critical determinant of virulence for
bacteria. The ability to attach to host cells allows bacteria to interact with
them in various ways, whether by type III secretion system or simply by holding on against the prevailing
movement of fluids. Outer membrane protein A (OmpA) has been shown to be
involved in the adherence of A. baumannii to epithelial cells. This
allows the bacteria to invade the cells through the zipper mechanism.
The protein
was also shown to localize to the mitochondria of epithelial cells and cause necrosis by
stimulating the production of reactive oxygen species.
Antibiotic resistance
Mechanisms of antibiotic resistance can be categorized
into three groups. First, resistance can be achieved by reducing membrane
permeability or increasing efflux of the antibiotic and thus preventing access
to the target. Second, bacteria can protect the antibiotic target through
genetic mutation or post-translational modification, and last, antibiotics can
be directly inactivated by hydrolysis or modification. One of the most
important weapons in the armoury of Acinetobacter is its impressive genetic
plasticity, facilitating rapid genetic mutations and rearrangements as well as
integration of foreign determinants carried by mobile genetic elements. Of
these, insertion sequences are considered one of the key forces shaping
bacterial genomes and ultimately evolution.
AbaR resistance
islands
Pathogenicity islands, relatively common genetic structures in bacterial
pathogens, are composed of two or more adjacent genes that increase a
pathogen's virulence. They may contain genes that encode toxins, coagulate blood, or as in this case, allow the bacteria to resist antibiotics. AbaR-type
resistance islands are typical of drug-resistant A. baumannii, and
different variations may be present in a given strain. Each consists of a transposon backbone of about 16.3 Kb that facilitates horizontal gene transfer. This makes horizontal gene transfer of this and similar pathogenicity
islands more likely because, when genetic material is taken up by a new
bacterium, the transposons allow the pathogenicity island to integrate into the
new microorganism genome. In this case, it would grant the new microorganism
the potential to resist certain antibiotics. Antibiotic resistance genes are
commonly transferred between Gram-negative bacteria through plasmids via
conjugation, which accelerates the appearance of new resistant strains. AbaR's
contain several genes for antibiotic resistance, all flanked by insertion seqsuence. There exist several resistance genes circulating
along A. baumannii that can be clustered in replicon groups, and may
be transferred from the extensively drug-resistant Acinetobacter
baumannii (XDR- AB) and New Delhi Metallo-beta-lactamase-1-producing Acinetobacter
baumannii (NDM- AB) to environmental isolates
of Acinetobacter spp. Conjugation experiments demonstrated that
the blaOXA-23, blaPER-1, and aphA6 genes could be successfully
transferred between the clinical and the environmental isolates via the plasmid
group GR6 or class 1 integrons through in vitro conjugation. In collaboration with some other genes, they
provide resistance to aminoglycosides, aminocyclitols, tetracycline, and chloramphenicol.
Efflux pumps
Efflux pumps are protein machines that use energy to pump antibiotics and other small
molecules that get into the bacterial cytoplasm and the periplasmic
space out of the
cell. By constantly pumping antibiotics out of the cell, bacteria can increase
the concentration of a given antibiotic required to kill them or inhibit their
growth when the target of the antibiotic is inside the bacterium. A.
baumannii is known to have two major efflux pumps which decrease its
susceptibility to antimicrobials. The first, AdeB, has been shown to be
responsible for aminoglycoside resistance. The second, AdeDE, is responsible for efflux of a
wide range of substrates, including tetracycline, chloramphenicol, and various
carbapenems. Many other efflux pumps have been implicated
in A. baumannii resistant strains.
Small RNA
Bacterial small RNAs are noncoding RNAs that regulate various cellular
processes. Three sRNAs, AbsR11, AbsR25, and AbsR28, have been experimentally
validated in the MTCC 1425 (ATCC15308) strain, which is a (multidrug-resistant) strain showing resistance to 12 antibiotics. AbsR25
sRNA could play a role in the efflux pump regulation and drug resistance.
Beta-lactamase
A.
baumannii has been shown to produce at least one beta-lactamase, which is an enzyme responsible for cleaving the
four-atom lactam ring typical of beta-lactam antibiotics. Beta-lactam antibiotics are structurally related to penicillin, which inhibits synthesis of the bacterial cell wall. The cleaving of the lactam ring renders these
antibiotics harmless to the bacteria. A. baumannii have been observed
to express beta-lactmases known as Acinetobacter-derived cephalosporinases
(ADCs), which are class C beta-lactamases. In addition, the beta-lactamase OXA-51, a class D
beta-lactamase, has been observed in A. baumannii, found to be flanked by
insertion sequences, suggesting it was acquired by horizontal gene transfer.
Biofilm formation
A. baumannii has been noted for its apparent ability
to survive on artificial surfaces for an extended period of time, therefore
allowing it to persist in the hospital environment. This is thought to be due
to its ability to form biofilms. For many biofilm-forming bacteria, the process is mediated by
flagella. However, for A. baumannii, this process seems to be mediated by
pili. Further, disruption of the putative pili chaperone and usher
genes csuC and csuE were shown to inhibit biofilm formation. The formation of biofilms has been shown to alter
the metabolism of microorganisms within the biofilm, consequently reducing
their sensitivity to antibiotics. This may be because fewer nutrients are
available deeper within the biofilm. A slower metabolism can prevent the
bacteria from taking up an antibiotic or performing a vital function fast
enough for particular antibiotics to have an effect. They also provide a
physical barrier against larger molecules and may prevent desiccation of the
bacteria. In general, biofilm formation has been linked so
far with BfmRS TCS (two-component system) regulating Csu pili, Csu expression
regulated by the GacSA TCS, biofilm-associated proteins BapAb, synthesis of the
exopolysaccharide poly-β-1,6-N-acetylglucosamine PNAG, acyl-homoserine lactones
through AbaR receptor, and AbaI autoinducer synthase. Moreover, inactivation of adeRS operon
negatively affects biofilm formation and prompts decreased expression of
AdeABC. Disruption of abaF has displayed an increase in fosfomycin
susceptibility and a decrease in biofilm formation and virulence, suggesting a
major role for this pump.
Signs and symptoms of infection
A. baumannii is an opportunistic pathogen with a
range of different diseases, each with their own symptoms. Some possible types
of A. baumannii infections include:
·
Pneumonia
·
Bloodstream infections
·
Wound and surgical site infections, including necrotizing fasciitis
Symptoms of A. baumannii infections are often indistinguishable from other opportunistic infections caused by other opportunistic bacteria - including Klebsiella pneumoniae and Streptococcus pneumoniae.
Symptoms of A. baumannii infections in turn
range from fevers and chills, rash, confusion and or altered mental states,
pain or burning sensations when urinating, strong urge to urinate frequently, sensitivity
to bright light, nausea (with or without vomiting), muscle and chest pains,
breathing problems, and cough (with or without yellow, green, or bloody mucus). In some cases, A. baumannii may present
no infection or symptoms, as with colonizing an open wound or tracheostomy.
Treatment
When infections are caused by antibiotic-susceptible
Acinetobacter isolates, there may be several therapeutic options, including a
broad-spectrum cephalosporin (ceftazidime or cefepime), a combination
beta-lactam/beta-lactamase inhibitor (ie, one that includes sulbactam), or a
carbapenem (eg, imipenem or meropenem). Because most infections are now
resistant to multiple drugs, determining what susceptibilities the particular
strain has is necessary for treatment to be successful. Traditionally,
infections were treated with imipenem or meropenem, but a steady rise in carbapenem-resistant A. baumannii has been noted. Consequently, treatment methods often fall back ,
particularly colistin although tetracyclines have shown promise in MDR A. baumannii. Colistin is considered a drug of last resort
because it often causes kidney damage, among other side effects. Prevention methods in hospitals focus on increased
hand-washing and more diligent sterilization procedures. An A. baumannii infection was recently
treated using phage therapy. Phages are viruses that attack bacteria, and have also been demonstrated to
resensitize A. baumannii to antibiotics it normally resists.
Traumatic injuries,
like those from improvised explosive devices, leave large open areas
contaminated with debris that are vulnerable to becoming infected with A.
baumannii.
The logistics of
transporting wounded soldiers result in patients visiting several facilities
where they may acquire A. baumannii infections.
Scientists at MIT, Harvard's Broad Institute and MIT's CSAIL found a compound named halicin using deep learning that can effectively kill A. baumannii. The compound is a repurposed drug.
Occurrence in veterans injured in Iraq and Afghanistan
Soldiers in Iraq and Afghanistan are at risk for
traumatic injury due to gunfire and improvised explosive devices. Previously, infection was thought to occur due to
contamination with A. baumannii at the time of injury. Subsequent
studies have shown, although A. baumannii may be infrequently
isolated from the natural environment, the infection is more likely
nosocomially acquired, likely due to the ability of A. baumannii to
persist on artificial surfaces for extended periods, and the several facilities
to which injured soldiers are exposed during the casualty-evacuation process.
Injured soldiers are first taken to level-I facilities, where they are
stabilized. Depending on the severity of the injury, the soldiers may then be
transferred to a level-II facility, which consists of a forward surgical team,
for additional stabilization. Depending on the logistics of the locality, the
injured soldiers may transfer between these facilities several times before
finally being taken to a major hospital within the combat zone (level III).
Generally after 1–3 days, when the patients are stabilized, they are
transferred by air to a regional facility (level IV) for additional treatment.
For soldiers serving in Iraq or Afghanistan, this is typically Landstuhl Regional Medical Center in Germany. Finally, the injured soldiers are transferred to
hospitals in their home country for rehabilitation and additional treatment. This repeated exposure to many different medical
environments seems to be the reason A. baumannii infections have
become increasingly common. Multidrug-resistant A. baumannii is a
major factor in complicating the treatment and rehabilitation of injured
soldiers, and has led to additional deaths.
Incidence in hospitals
Being referred to as an opportunistic infection, A.
baumannii infections are highly prevalent in hospital settings. A.
baumannii poses very little risk to healthy individuals; however,
factors that increase the risks for infection include:
·
Having a weakened immune system
·
Chronic lung disease
·
Diabetes
·
Lengthened hospital stays
·
Illness that requires use of a hospital ventilator
·
Having an open wound treated in a hospital
·
Treatments requiring invasive devices like urinary catheters
·
A. baumannii can be spread through direct contact
with surfaces, objects, and the skin of contaminated persons.
The importation of A. baumannii and subsequent
presence in hospitals has been well documented. A. baumannii is usually introduced into a
hospital by a colonized patient. Due to its ability to survive on artificial
surfaces and resist desiccation, it can remain and possibly infect new patients
for some time. A baumannii growth is suspected to be favored in
hospital settings due to the constant use of antibiotics by patients in the
hospital. Acinetobacter can be spread by person-to-person
contact or contact with contaminated surfaces. Acinetobacter can enter through open wounds,
catheters and breathing tubes. In a study of European intensive care units in
2009, A. baumannii was found to be responsible for 19.1% of
ventilator-associated pneumonia cases.
Jan Ricks Jennings, MHA, LFACHE
Senior Consultant
Senior Management Resources, LLC
412.913,0636 Cell
724.733.0509 Office
JanJenningsBlog.Blogspot.com
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