Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. 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.
A coccobacillus is a type of bacterium with a shape intermediate between cocci and bacilli. Coccobacilli, then, are very short rods which may be mistaken for cocci.
Acinetobacter is a genus of Gram-negative bacteria belonging to the wider class of Gammaproteobacteria. Acinetobacter species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification.
Soil is a mixture of organic matter, minerals, gases, liquids, and organisms that together support life. Earth's body of soil, called the pedosphere, has four important functions:
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 forward.Clinical microbiologists typically differentiate members of the genus Acinetobacter from other Moraxellaceae by performing an oxidase test, as Acinetobacter spp. are the only members of the Moraxellaceae to lack cytochrome c oxidases.
A pilus is a hair-like appendage found on the surface of many bacteria. The terms pilus and fimbria can be used interchangeably, although some researchers reserve the term pilus for the appendage required for bacterial conjugation. All pili in the latter sense are primarily composed of pilin proteins, which are oligomeric.
Relative molecular mass or molecular weight is the mass of a molecule. It is calculated as the sum of the relative atomic masses of each constituent element multiplied by the number of atoms of that element in the molecular formula. The molecular mass of small to medium size molecules, measured by mass spectrometry, determines stoichiometry. For large molecules such as proteins, methods based on viscosity and light-scattering can be used to determine molecular mass when crystallographic data are not available.
The Moraxellaceae are a family of Gammaproteobacteria, including a few pathogenic species. Others are harmless commensals of mammals and humans or occur in water or soil. The species are mesophilic or psychrotrophic (Psychrobacter).
A. baumannii is part of the ACB complex (A. baumannii, A. calcoaceticus, and Acinetobacter genomic species 13TU). Members of the ACB complex are difficult to determine the specific species and 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.
ESKAPE is an acronym encompassing the names of six bacterial pathogens commonly associated with antimicrobial resistance: ESKAPE is an acronym for their names and a reference to their ability to escape the effects of commonly used antibiotics through evolutionarily developed mechanisms, and also because it is a acronym for their names.
Enterococcus faecium is a Gram-positive, alpha-hemolytic or non-hemolytic bacterium in the genus Enterococcus. It can be commensal in the gastrointestinal tract of humans and animals, but it may also be pathogenic, causing diseases such as neonatal meningitis or endocarditis.
Staphylococcus aureus is a Gram-positive, round-shaped bacterium that is a member of the Firmicutes, and it is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe that can grow without the need for oxygen. Although S. aureus usually acts as a commensal of the human microbiota it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. The emergence of antibiotic-resistant strains of S. aureus such as methicillin-resistant S. aureus (MRSA) is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.
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.
The Iraq War was a protracted armed conflict that began in 2003 with the invasion of Iraq by a United States-led coalition that overthrew the government of Saddam Hussein. The conflict continued for much of the next decade as an insurgency emerged to oppose the occupying forces and the post-invasion Iraqi government. An estimated 151,000 to 600,000 or more Iraqis were killed in the first three to four years of conflict. The U.S. became re-involved in 2014 at the head of a new coalition; the insurgency and many dimensions of the civil armed conflict continue. The invasion occurred as part of a declared war against international terrorism and its sponsors under the administration of U.S. President George W. Bush following the September 11 terrorist attacks.
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 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.
Adhesins are cell-surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces, usually the host they are infecting or living in. Adhesins are a type of virulence factor.
Type three secretion system is a protein appendage found in several Gram-negative bacteria.
Reactive oxygen species (ROS) are chemically reactive chemical species containing oxygen. Examples include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
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. Transposons allow portions of genetic material to be excised from one spot in the genome and integrate into another. 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's genome. In this case, it would grant the new microorganism the potential to resist certain antibiotics. AbaRs contain several genes for antibiotic resistance, all flanked by insertion sequences. These genes provide resistance to aminoglycosides, aminocyclitols, tetracycline, and chloramphenicol.
Pathogenicity islands (PAIs), as termed in 1990, are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. Pathogenicity islands are found in both animal and plant pathogens. Additionally, PAIs are found in both gram-positive and gram-negative bacteria. They are transferred through horizontal gene transfer events such as transfer by a plasmid, phage, or conjugative transposon. Therefore, PAIs contribute to microorganisms' ability to evolve.
Virulence is a pathogen's or microbe's ability to infect or damage a host.
A toxin is a poisonous substance produced within living cells or organisms; synthetic toxicants created by artificial processes are thus excluded. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived from the word toxic.
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.
Bacterial small RNA s 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.
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. The beta-lactamase OXA-51 was found to be flanked by insertion sequences, suggesting it was acquired by horizontal gene transfer.
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.
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:
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 site.
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 on polymyxins, particularly colistin. 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. Acinetobacter baumannii was recently treated using phages (anti-bacterial viruses).
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.
Being referred to as an opportunistic infection, A. baumanii infections are highly prevalent in hospital settings. A. baumanii poses very little risk to healthy individuals,however, factors that increase the risks for infection include
A. baumanii 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.
A 2013 Indonesian study showed that neonatal infections with A. baumanii were due to the same strains of the bacteria found in the hospital in which the neonates had spent their earliest days. These strains were found on hard surfaces as well as on the hands of medical personnel.
An antibiotic is a type of antimicrobial substance active against bacteria and is the most important type of antibacterial agent for fighting bacterial infections. Antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics.
Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The immune system of an organism is in essence a drug deliverythe system.
Colistin, also known as polymyxin E, is an antibiotic produced by certain strains of the bacteria Paenibacillus polymyxa. Colistin is a mixture of the cyclic polypeptides colistin A and B and belongs to the class of polypeptide antibiotics known as polymyxins. Colistin is effective against most Gram-negative bacilli.
Meropenem, sold under the brandname Merrem among others, is a broad-spectrum antibiotic used to treat a variety of bacterial infections. Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax. It is given by injection into a vein.
Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to multiple antimicrobial drugs. The types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, parasites. Recognizing different degrees of MDR, the terms extensively drug resistant (XDR) and pandrug-resistant (PDR) have been introduced. The definitions were published in 2011 in the journal Clinical Microbiology and Infection and are openly accessible.
Tigecycline is an antibiotic for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resistant bacteria such as Staphylococcus aureus, Acinetobacter baumannii, and E. coli. As a tetracycline derivative antibiotic, its structural modifications has expanded its therapeutic activity to include Gram-positive and Gram-negative organisms, including those of multi-drug resistance.
Pseudomonas aeruginosa is a common encapsulated, Gram-negative, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes.
Carbapenems are a class of highly effective antibiotic agents commonly used for the treatment of severe or high-risk bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta lactam class of antibiotics, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.
Imipenem is an intravenous β-lactam antibiotic discovered by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the β-lactamase enzymes produced by many multiple drug-resistant Gram-negative bacteria, thus play a key role in the treatment of infections not readily treated with other antibiotics.
Klebsiella pneumonia (KP) is a form of bacterial pneumonia associated with Klebsiella pneumoniae. It is typically due to aspiration and alcoholism may be a risk factor, though it is also commonly implicated in hospital-acquired urinary tract infections, and COPD individuals
Arbekacin (INN) is a semisynthetic aminoglycoside antibiotic. It is primarily used for the treatment of infections caused by multi-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Arbekacin was originally synthesized from dibekacin in 1973. It has been registered and marketed in Japan since 1990 under the trade name Habekacin. Arbekacin is no longer covered by patent and generic versions of the drug are also available under such trade names as Decontasin and Blubatosine.
Multidrug tolerance or antibiotic tolerance is the ability of a disease-causing microorganism to resist being killed by antibiotics or other antimicrobials. It is mechanistically distinct from multidrug resistance: It is not caused by mutant microbes, but rather by microbial cells that exist in a transient, dormant, non-dividing state. Microorganisms that display multidrug tolerance can be bacteria, fungi or parasites.
New Delhi metallo-beta-lactamase 1 (NDM-1) is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. These include the antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections. The gene for NDM-1 is one member of a large gene family that encodes beta-lactamase enzymes called carbapenemases. Bacteria that produce carbapenemases are often referred to in the news media as "superbugs" because infections caused by them are difficult to treat. Such bacteria are usually susceptible only to polymyxins and tigecycline.
Multidrug resistant Gram-negative bacteria are a type of Gram-negative bacteria with resistance to multiple antibiotics. They can cause bacteria infections that pose a serious and rapidly emerging threat for hospitalized patients and especially patients in intensive care units. Infections caused by MDR strains are correlated with increased morbidity, mortality, and prolonged hospitalization. Thus, not only do these bacteria pose a threat to global public health, but also create a significant burden to healthcare systems.
Carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae (CPE) are Gram-negative bacteria that are resistant to the carbapenem class of antibiotics, considered the drugs of last resort for such infections. They are resistant because they produce an enzyme called a carbapenemase that disables the drug molecule. The resistance can vary from moderate to severe. Enterobacteriaceae are common commensals and infectious agents. Experts fear CRE as the new "superbug". The bacteria can kill up to half of patients who get bloodstream infections. Tom Frieden, former head of the Centers for Disease Control and Prevention has referred to CRE as "nightmare bacteria". Types of CRE are sometimes known as KPC and NDM. KPC and NDM are enzymes that break down carbapenems and make them ineffective. Both of these enzymes, as well as the enzyme VIM have also been reported in Pseudomonas.
Plazomicin is a next-generation aminoglycoside ("neoglycoside") antibacterial derived from sisomicin by appending a hydroxy-aminobutyric acid (HABA) substituent at position 1 and a hydroxyethyl substituent at position 6'.
Resistance-nodulation-division (RND) family transporters are a category of bacterial efflux pumps, especially identified in Gram-negative bacteria and located in the cytoplasmic membrane, that actively transport substrates. The RND superfamily includes seven families: the heavy metal efflux (HME), the hydrophobe/amphiphile efflux-1, the nodulation factor exporter family (NFE), the SecDF protein-secretion accessory protein family, the hydrophobe/amphiphile efflux-2 family, the eukaryotic sterol homeostasis family, and the hydrophobe/amphiphile efflux-3 family. These RND systems are involved in maintaining homeostasis of the cell, removal of toxic compounds, and export of virulence determinants. They have a broad substrate spectrum and can lead to the diminished activity of unrelated drug classes if over-expressed. The first reports of drug resistant bacterial infections were reported in the 1940s after the first mass production of antibiotics. Most of the RND superfamily transport systems are made of large polypeptide chains. RND proteins exist primarily in gram-negative bacteria but can also be found in gram-positive bacteria, archaea, and eukaryotes.