The Superbug Threat
By Subashini Amalraj B.D.S, Medical Writer
"Bacteria Run Wild, Defying Antibiotics" Puzzling the Experts....
Superbug has been characterized as an antibiotic resistant organism. This highly resistant organism carries a gene that produces an enzyme which renders the antibiotics futile. The superbug gene can be transferred between bacteria in horizontal fashion through chromosomes and plasmids.
Bacteria have developed resistance to most of the known antibiotics for many decades - penicillin resistance in the 1950s followed by methicillin resistance in the 1980s and vancomycin resistance in the 1990s.
The threat caused by the newly emerged gram negative superbugs - NDM-1 (New Delhi metallo-beta-lactamase-1) and CRKP (Carbapenem-Resistant Klebsiella pneumoniae) are worse than that of our old gram positive bugs – Methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile and other extended-spectrum beta-lactamase (ESBL) organisms.
NDM-1 is a new type of acquired metallo-beta-lactamases (MBLs). MBL producing strains are commonly isolated from urine, blood, bronchial secretions and other sources such as surgical wound, skin and soft tissue, pleural fluid, CSF, peritoneal fluid, bile, bone, stool, catheter tips and drains.
NDM-1 is an enzyme produced by certain strains of bacteria. It was first detected in Klebsiella pneumoniae isolated from a Swedish patient when hospitalized in New Delhi. This enzyme is active against the compounds that contain a chemical structure known as the beta-lactam ring. Unfortunately, many antibiotics contain this ring, including the penicillins, cephalosporins and the carbapenems.
Klebsiella pneumoniae which can invade the lungs and the gut bacterium Escherichia coli are the currently known bacteria hosting this gene. Bacteria in association with this NDM-1 gene produce E.Coli and Klebsiella pneumoniae infections, urinary tract infections, respiratory tract infections, intra-abdominal infections and bacteremia leading to shock.
Even more alarmingly, NDM-1 is no lone threat – it comes as part of a family. Similar enzymes in the same class, known as carbapenemases, have been detected. CRKP (Carbapenem-Resistant Klebsiella pneumoniae) is the current superbug, which created a large outbreak in Los Angeles, spreading worldwide. Those enzymes are far more common than bacteria carrying the gene NDM-1.
Unlike other superbugs such as MRSA, the CRKP pathogen is an enterobacterium, in the same "lethal family" of bacteria as E. coli. They are equipped with a gene that enables them to produce an enzyme called KPC (Klebsiella pneumoniae carbapenamase) which immobilizes even the most powerful antibiotics, the Carbapenems.
Carbapenem-Resistance Enterobacteriaceae (CRE) infections occurs by many mechanisms, one of which is the production of metallo-beta-lactamase (such as NDM, VIM, and IMP) or a carbapenemase (such as KPC). These infections have ranged from mild to severe and even fatal up to 30 - 60 percent of cases.
Patients at risk:
- Several co-morbidities
- History of surgery
- Admitted to ICUs
- Neonates with low birth weight in neonatal ICUs
- Prolonged hospitalization, antineoplastic chemotherapy, long term use of corticosteroids
- Increased duration and high total dose of antibiotics
"Superbugs and Superdrugs"
A common way of treating the severe form of ESBL infections is the use of carbapenem, which becomes the drug of choice as it has the lowest resistance rate and the broadest mechanism of action against Gram-negative infections; however the superbugs have developed resistance against this last line of defense also.
What makes the superbugs so dangerous is not only its ability to outflank carbapenems, but also the company it keeps, the tough bacteria which is already resistant to many other antibiotics.
The antibiotics shown to work against the superbugs are tigecycline, polymyxin B, or polymyxin E (colistin). They were the only drugs that could combat the superbugs effectively; however polymyxins were abandoned due to its toxic effect on the kidneys. Discovery of new drugs against NDM 1-producing bacteria or the other superbugs are in the clinical trial stage.
Prevention is Crucial
Measures undertaken by the World Health Organization (WHO):
Surveillance for antimicrobial resistance.
Rational antibiotic use, including education of healthcare workers and the public in the appropriate use of antibiotics.
Introducing or enforcement of legislation related to stop selling of antibiotics without a prescription.
Strict adherence to infection prevention and control measures, including the use of hand-washing measures, particularly in healthcare systems.
The Infectious Disease Society of America has launched a “bad bugs need drugs” campaign to promote the development of new antibiotics by 2020.
The Superbug phenomenon is an alarming concept, which could disseminate worldwide very quickly and originate a wide and uncontrollable spread of pandemic clones for which new and effective antibiotics are currently not available. This suggests that NDM 1 and its relatives are not in fact, the ultimate "super superbugs" but rather just the tip of the iceberg.
“Superbugs are visible manifestations of our prolonged failure to use antibiotics rationally”
Read more about it:
www.thelancet.com/journals/.../article/PIIS1473-3099(10)70143-2
http://evolution.berkeley.edu/evolibrary/news/080401_mrsa
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1127417
http://www.ncbi.nlm.nih.gov/pubmed/15673804