This year 2010 marks another significant turn in the war against microbes. An August 11, 2010 report in The Lancet indicates that medicine has lost an important bacterial infectious disease battle and humans are at risk now more than ever. These new antibiotic-resistant enteric bacteria contain NDM 1 Beta Lactamase. This is no false alarm, nor minor claim – it is a very real, clear and present danger. The background of antibiotic resistance and The Lancet paper are overviewed and summarized here for important facts and details on these superbugs. The CDC also provides antimicrobic and antimicrobial insights.
Bacteria, Antibiotics and Resistance – Facts and Definitions
To better understand the issues involved with NAD 1 Beta lactamases here are some important terms and definitions:
- Bacteria (bacterium, sing.) – Single-celled, primitive cells with a simple nucleus without a membrane. Each bacterium contains about 1,000 genes
- Gram-positive Bacteria – bacteria which appear purple-blue when stained with the Gram stain (e.g., Staphylococcus, Streptococcus, Clostridium)
- Gram-negative Bacteria– bacteria which stain red when Gram stained (e.g., Escherichia, Enterobacter, Klebsiella, Pseudomonas)
- Antibiotics – biochemicals normally produced naturally by certain microbes to inhibit or kill other microbes. Antibiotics are isolated in the lab, purified and tested for effectiveness and safety for use in animals and humans
- Semi-synthetic and Synthetic Antibiotics – are chemically-modified or synthesized antibiotics that are produced in special chemical reaction vessels
- DNA – a macromolecule and double helix that contains nucleotides (chemical code sequences) called genes for the manufacture of specific kinds of proteins
- Chromosome – a double helix of DNA and associated protein
- Gene – a DNA code that specifies the order and kinds of amino acids needed to make proteins.
- Plasmids – segments or circles of DNA that are not part of the bacterial chromosome
- Resistance Genes – DNA information on chromosomes or plasmids, or both, that code or instruct for factors, products or enzymes that can block, impede, inactivate or destroy antibiotics
- Beta Lactamases – powerful enzymes that can break and destroy the structural beta-lactam ring of some of the most important types antibiotics (penicillins, cephalosporins, carbapenems)
- Kirby-Bauer-Sherris Antibiotic Susceptibility Test – Concentrated antibiotic disks are placed on special agar (Mueller-Hinton) covered with a layer of a pure culture of the test bacterium. After 24-hr incubation, the inhibitory zone sizes on agar are measured to determine whether the test bacteria are S (Susceptible), R (Resistant) or I (Indeterminate or Intermediate). These tests permit determinations and correlations of zone sizes with the actual MIC (minimum inhibitory concentrations) of antibiotics in liquid media.
Beta Lactamase NDM 1 and Bacterial Resistance
The New Delhi, India, Pakistan and U.K. enterics have a carbapenemase gene carried on plasmids which is a metallo-β-lactamase 1 or NDM 1. The multi-city, multi-investigator research is reported in The Lancet medical journal and the following findings are significant:
- The NDM-1 resistance gene is on plasmids (extranuclear DNA) that can be exchanged among enterics.
- These resistance plasmids can be isolated, characterized and identified.
- Most NDM 1 bacteria contain several plasmids and up to 8 plasmids have been isolated from some cells.
- Many common enteric bacteria such as Escherichia, Klebsiella, Enterobacter, Proteus, Citrobacter, Providencia, Morganella contain these plasmids.
- NDM-1 resistant enterics are common both in outside communities and hospitals in India.
- These mutant and antibiotic-resistant bacteria have been cultivated by excessive and indiscriminate use of many non-prescription antibiotics throughout the Indian population.
- Patients and travelers to the U.K. may have acquired these NDM 1 strains of bacteria and brought them back to the U.K. The infections may be acquired in the community or the hospital environments.
- Citizens in India's and Pakistan's many large cities harbor enterics with NDM 1. Even Dhaka, Bangladesh is positive for these strains.
- NDM 1 enterics have been isolated from patients with urinary tract infections, pneumonia, blood stream infections (bactermias/septicemias), burns, and wounds. Other tissues and organs may become infected with these enterics.
- Infection occurs in females:males at a ratio of about 2:1. Persons of all ages are susceptible to these infections and diseases.
- Resistance to amikacin, tobramycin, ciprofloxacin, and gentamicin is very high. Only colistin and tigecycline show reasonable effectiveness against these NDM 1 strains.
- New outbreaks of NDM 1 resistant strains may occur in other cities and countries and medical alerts for this possibility are in order.
- The CDC in Atlanta, Georgia has reported in the MMWR on 3 cases of these drug-resistant bacteria in 3 different states, during the period Jan to June 2010 (Detection of Enterobacteriaceae Isolates Carrying Metallo-Beta-Lactamase — United States, 2010). These 3 cases could be traced back to patients who were medically-treated in India.
A somber sentence from Dr. Kumarasamy and his 30 collaborators in The Lancet paper is:
"Enterobacteriaceae with NDM-1 carbapenemases are highly resistant to many antibiotic classes and potentially herald the end of treatment with β-lactams, fluoroquinolones, and aminoglycosides—the main antibiotic classes for the treatment of Gram-negative infections."
Sources
CDC. Antibiotic / Antimicrobial Resistance. Accessed, 12 August, 2010
Dionisio, F. et al. "Plasmids Spread Very Fast in Heterogeneous Bacterial Communities." Genetics. 2002 December; 162(4): 1525–1532
Frieden, T.R. Antibiotic Resistance and the Threat to Public Health. U.S. House Hearings, Energy-Commerce Committee, Subcommittee on Health, Wednesday, 28 April 2010
Kumarasamy, K. et al. " Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study." The Lancet Infectious Diseases, Early Online Publication, 11 August 2010 doi:10.1016/S1473-3099(10)70143-2
Donald Reinhardt - Think, read, write & live well always. DJR has a PhD in Biology/Microbiology & is a Fellow & Diplomate, ASM Amer Acad Micro.
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