All About Antibiotic Resistance & Bacteria

Doctors are running out of antibiotics to treat some infections that can kill vulnerable people in the hospital and is rapidly spreading in the community infecting health adults and children. CDC published a statement “Children born after 2002 are more likely to die before their parents” is depressing for parents with children. WHO have estimated the number of people colonized with antibiotic resistant bacteria in the world to be around 53 million.

Experts are urging drug companies not to give up an area of research they consider unprofitable. Although the pharmaceutical industry have developed new antibiotics to treat the so-called hospital superbug MRSA (methycillin-resistant Staphylococcus aureus), the pipeline for drugs to treat some other infections was practically dry.

The cost of developing a new drug is usually said to be somewhere between $500m (£285m) and $1bn, depending on whether the many drugs that fail are costed in and whether the marketing budget is included.

Antibiotics were not a priority for the pharmaceutical industry, but they remained a critical area for public health. Most troubling now is the rise of what are known as gram negative bacteria (MRSA is gram positive) which are becoming resistant to antibiotics. These include E coli, which can cause serious food poisoning, Acinetobacter, which can kill those whose immune system is compromised, Streptococcus Pneumoniae Serotype 19A producing meningitis in immunised children and Pseudomonas, which particularly attacks cystic fibrosis patients.

Doctors and patients are advised to do their bit to prolong the life of antibiotics by not over-using them by Health Care Commission, NICE and the Politicians. NHS has published leaflets to educate patients not ask for them to treat coughs and colds, which are caused by viruses, not bacteria, but this policy is difficult to implement due to lack of support to doctors. Clinically it is difficult to differentiate viral from bacterial infections but the courts have penalised doctors when this mistake occurs. Patients confidence has been undermined and they do not trust doctor’s clinical hunch and so demand antibiotics. Saying no to antibiotic results in failed consultation and the doctors are blamed and victimised due to NHS complaint policy.

Resistance to antibiotics has now spread around the world in a way it did not in past decades. Fifty years ago, resistance that developed in India stayed in India but now it is here, unfortunately we are not prepared. Resistance is just evolution in real time. It just happens quicker with germs than in rats and humans. Penicillin's introduction in 1944, 50% of Staphylococcus aureus were resistant within six years. Tolerance was first described in S. aureus and has since been described with streptococci and enterococci.

Persistent Staphylococcus aureus bacteraemia is most frequently related to S. aureus acute bacterial endocarditic, myocardial abscess, extra cardiac abscess, or a device-associated infection. Patients with continuous high-grade bacteraemia who do not have acute bacterial endocarditis, an abscess, or a device-related infection should be considered to have antimicrobial "tolerance" as a possible cause. Antimicrobial "tolerance" is defined as a wide discrepancy between the minimal inhibitory concentration and the minimal bactericidal concentration of an isolate.

Despite apparent in vitro susceptibility, infections caused by "tolerant" strains are not cured by appropriate antimicrobial therapy. The lack of bactericidal activity of the antibiotic becomes apparent when minimal bactericidal concentrations are determined for "tolerant" strains, and there is a great discrepancy between the minimal inhibitory concentrations being used. Antibiotic tolerance to S. aureus has been described with a variety of antibiotics. To the best of our knowledge, this is the first case of continuous, high-grade methicillin-resistant S. aureus bacteraemia due to a linezolid-tolerant strain (1)

Two companies invested large sums of their R&D fund to fast track antibiotic development have failed to deliver. It is vital that the pharmaceutical industry remains interested in this area. Several major companies have pulled out of antibiotic development. They have not been seen as a particularly profitable area. If the pharmaceutical develop a new heart drug, the patient is on it for a matter of years and resistance doesn't develop. With antibiotics on the other hand, the patient is on it for one or two years and resistance may develop.

There are one or two drugs doctors can then use as a last resort, but they are either toxic or do not work well. Antibiotics have always had a limited lifespan because bacteria are proficient at evolving to survive. Pfizer’s introduced “Linezolid” in 2002 and has withdrawn this drug as high-grade methicillin-resistant S. aureus bacteraemia has developed tolerance. The last really effective drugs are the carbapanems, but the bacteria are increasingly showing resistance to them.

Alternatives to antibiotics, such as vaccines against specific bacterial infections, had been the subject of research but so far without a great deal of success. Staph Vac, developed in UK has not been successful as it offered immunity for only 45 days and is expensive. NHS is considering to use this as prophylactic measure before performing surgical procedure.

Doctors and patients can also do their bit to prolong the life of antibiotics by not over-using them. Health Protection Agency advice doctors should never prescribe them and patients should not ask for them to treat coughs and colds, which are caused by viruses, not bacteria.

Professor Peter Borriello, director of the HPA's centre for infections, pointed out that resistance now spread around the world in a way it did not in past decades. "Fifty years ago, resistance that developed in India stayed in India," he said. "Now it can be here that week." Resistance was inevitable, he said. "This is just evolution in real time. It just happens quicker with bacteria than in rats and humans."

The bacteria, and the infections they can cause, used to be confined mostly to surgical wounds in hospitals and chronic wounds in nursing homes. But now the same tough-to-kill bacteria are occurring in the community effecting healthy adults and children.

About 85% of MRSA infections can be traced back to a hospital stay and two-thirds occur after a patient has arrived back home. But 15% of the infections can't be linked to a hospitalization. That was the case for my construction worker.

Initially, many patients mistake the infection for a insect bite. The infection forms spots that look like pimples or boils, and it can deepen and then spread. Most of the time simple surgical drainage is all that's needed, but other times it becomes invasive and goes painfully deep into the surrounding tissues and even the blood stream.

In patients with cancer, diabetes, eczema, immuno-compromised due chemotherapy or steroids, infection spread rapidly all over the body. We all harbour skin bacteria. Some bugs are worse than others. About 25% to 30% of people carry staphylococcus aureus on the skin or in the nose and can pass it to others. Only about 1% of the population is walking around with MRSA. Institute of tropical medicine published a paper claiming "Kissing is better than shaking hands to reduce bacterial infections".

Even so, nearly 18,650 people died from MRSA infection and 94,000 others were seriously sickened in 2005, according to the Centres for Disease Control and Prevention.

Most hospitals have strict policies in place to ensure that the staff uses procedures in the fight this spreading hospital infections. Prevention is better than treatment. Finding drugs to cure MRSA infections is a challenge. Bacteria eventually outwit the antibiotics we throw at them. And there's always a need for new weapons against the resistant bugs.

Biocides, the bacteria-killing chemicals in disinfectants and antiseptics, are universally used in hospitals to clean surfaces, sterilise medical instruments and equipment, and decontaminate skin before surgery. At the right levels, the chemicals destroy most micro-organisms but if weak doses are used the bugs can survive and grow stronger. Bacteria have in-built protein pumps that expel many different toxic substances, antiseptics and antibacterial chemicals from their cells. These "efflux pumps" are known to remove antibiotics and make bugs drug-resistant. The CDC has voiced concern that antibacterial cleaning products may be making the situation worse by spurring the resistance of germs.

Researchers also exposed MRSA taken from the blood of patients to low concentrations of several biocides and bacteria-killing dyes. Allowing some of the bugs to survive with the low doses meant that mutants were created which could not be harmed by the chemicals. This discovery is bad news for hospitals, gyms & schools trying to tackle the spread of super bugs such as MRSA. And this explain why some find it so hard to rid themselves of diseases, despite repeated purges.

Recurring infections present a real challenge to doctors. The dry, flaky and irritated skin in a child with eczema is more than a painful irritation. It's also an open route for MRSA they carries on her skin to reach deeper tissues. The toddler already has multiple scars on their legs from the boils that form below the skin. Most break open and drain after a few days, but some of the larger ones have needed intervention.

Some doctors are trying forgotten methods (Potassium permangenet bathes) to disinfect her skin. This approach, recommended by her allergist, has helped cut down on some skin infections. Using concentrated alcohol and other chemicals can dry skin resulting in cracks and invasive form of infection that kill the patients. People infected with MRSA in their skin are desperately looking for miracle cure and have resorted to using Menuka honey, clay and various unconventional treatment. Infected people are isolated and confined to living indoor as prisoners in their own home (Watch Videos published in Youtube).

MRSA spreads easily in close quarters like classrooms, locker rooms, lunch rooms, massage parlours and tanning beds. Athletes should shower right after practice. The same goes for anyone using shared equipment at the gym. The basics of MRSA prevention are hand washing, wiping down surfaces and covering cuts. Keeping personal care items separated from others also helps.

Around the office, disinfectants like bleach are often used more than antibacterial cleaners. Scientists say hospital bacteria which can survive an attack by disinfectants and antiseptics are becoming ultra-resistant superbugs.They have also discovered that if too low concentrations of antibiotics are used to kill such bugs in patients, mutations were created that could not be killed by drugs.

Study leader Dr Glenn Kaatz, from the Department of Veterans Affairs Medical Centre in Detroit, USA, said: "Because the efflux pumps also rid the cell of some antibiotics, pathogenic bacteria with more pumps are a threat to patients as they could be more resistant to treatment."

Bacteria have a basic survival strategy: to colonize surfaces and grow as bio-films communities embedded in a gel-like poly-saccharide matrix. There is no clear figure for how many people hospital infections such MRSA kills, but it is estimated to be as many as 5,000 a year.

A Department of Health spokesman said: "Antibiotic resistance is a global public health issue and we all have a part to play in keeping our antibiotics effective.

"Bacteria will always try to find ways to survive by evolving and developing resistance to antibiotics so we must stay ahead of the game.

Cannulation involves a needle being used to insert a tiny, flexible plastic sheath under the skin. The needle is then removed and the medicine or fluids can be introduced through the sheath, which remains in the blood vessels just under the skin.

Patients who were likely to need IV fluids or drugs in this way were given a cannula as a routine part of their medical care. As well as its new cannulation procedures, the trust is implementing hand hygiene audits and deep cleaning as ordered by the NHS.

The number of both community acquired and hospital acquired staphylococcal infection has increased in the past twenty years and this trend parallels the increased use of peripheral intravascular catheters (cannula) (4). Cannulae more often called “Venfon” are inserted in the emergency department, had a shorter duration from insertion to bacteraemia, and had Staphylococcus aureus more frequently as the causative pathogen (6). A primary cause of Staph infection in hospitals is the use of cannula (7). Infections can occur in several different ways, including: contamination of the device by skin flora on insertion, migration down the cannula tract from the skin, contamination through the hub during manipulation and seeding from another infection site.

The number of both community acquired and hospital acquired staphylococcal infection has increased in the past twenty years and this trend parallels the increased use of peripheral intravascular catheters (cannula). A primary cause of Staph infection in hospitals is the use of cannula. Majority of septicaemia begin with colonization of the cannula-insertion tract by bacteria from patients own skin-flora. Doctors and nurses introducing cannula do wash their hands but the scrubbing technique is usually ignored and they are advised to use un-sterile gloves.

Tougher rules on the use of intravenous cannula have been shown to cut the incidence of MRSA infections. Winchester and Eastleigh Healthcare NHS Trust (UK) has instead begun prescribing the insertion of cannulae. Doctors are able to monitor the tubes more closely for signs of infection. The trust said since the introduction last November there have been no new cases of MRSA infections.

This figure covers all forms of MRSA, including bloodstream infections (also known as bacteraemia) and wound infections. This compares to 2007/08 when there was 11 reported bloodstream infections.

Implementing these changes in every hospital is practically and ethically unacceptable. This illustrates that simple measures, like proper skin preparation, observe drying time, reducing the number of attempts and avoiding ported cannula when strictly followed, can work. We could reduce the spread of antibiotic resistant bacteria in our hospitals.

The staff are not identifying and locating the vein or artery prior to washing their hands. They are advised to wear an un-sterile glove to save cost. These gloves offer protection to staff but does not reduce the risk of introducing infection to patients. Staff introducing a cannula often searches for a good vein to introduce cannula needle use disinfectants on the skin and start palpating to identify a vein to puncture through the skin. They often palpate 2-3 locations before they puncture the skin and strict aseptic technique are not followed.

CDC guidelines and observing “Drying time” (wait for 1 -2 minutes after applying biocides). This may explain why some find it so hard to rid themselves of diseases, despite repeated purges Biocides, the bacteria-killing chemicals in disinfectants and antiseptics, are universally used in hospitals to decontaminate skin before performing this common procedure has developed tolerance. Doctors and nurse are not following. At the right levels, the chemicals destroy most micro-organisms but if weak doses are used the bugs can survive and is often introduced through the skin into blood vessels.

Multiple attempts to introduce cannula are traumatic and increase the incidence of introducing infections because adequate skin preparation is not often good in subsequent attempts. Vascular access is essential in neonatal units, paediatric units, A&E, ITU & Anaesthesiology. Introducing cannula is said to be the most common minor surgical procedure practiced in medicine. 80% of in-patients receive treatment via a cannula during their stay in the hospital. Since this technique was introduced in 1954, the procedure has been a daunting, stressful to patients and doctors. Most doctors claim to introduce a cannula in the second attempt but our observational study show that doctors need on average three attempts to successfully introduce a cannula in the vein. Use of ported cannula to access vein was banned in USA since studies demonstrated 50% of in-patients developed bacteraemia.

Multiple attempts to introduce cannula

NHS in UK continues to use seventeen million ported cannula ever year. With a contamination rate often as high as 50%, stopcocks (ports / hub) - used for medication injection, I.V. infusion administration, and blood sample collection-represent a potential entry portal for pathogens (14). Majority of septicaemia begin with colonization of the cannula-insertion tract by bacteria from patients own skin-flora (8). Mayo Clinic Proceedings: The results show that all types of IVDs pose a risk of bloodstream infection (BSI) and can be used for benchmarking rates of infection caused by the various types of IVDs in use at the present time (9).

Chhadia, AM et al; published the result of their study CA-MRSA Hand Infections in an Urban Setting, claiming 73% of healthy adults are said to carry this organism on their hands (10). Up to 41% of healthcare worker’s hands sampled (after patient care and before hand hygiene) were positive for VRE1 (11). Hand washing by hospital staff is said to be poor. Surgical hand hygiene (or antisepsis) can be performed by using either an antimicrobial soap OR an alcohol-based hand rubs with persistent activity. When an antimicrobial soap is used, the hands and forearms should be scrubbed for the length of time recommended by the product’s manufacturer, usually 2-6 minutes.

Chhadia, AM; A-MRSA Hand Infections in an Urban Setting,

Unfortunately, few clinical events have been observed in individual studies, it remains unclear which antiseptic solution is best, both statistically and clinically, for reducing the risk for catheter-related blood stream infection (15). One study found 40% of workers do not adequately wash their hands well before performing a practical invasive procedure in patients (13). This coupled with 53%-70% of health adults colonising antibiotic resistant bacteria in their hand (10) and resistance to biocides is likely to increases the chances of introducing bacteria into blood stream resulting in serious systemic infection. Using non-sterile gloves when cannulation does not prevent introduction of infection.

Peripheral vascular cannulae inserted in the emergency department caused the highest number of episodes and had a shorter duration to bacteraemia than those inserted in other hospital areas. This is probably due to the fact that in the emergency department, cannulae are used excessively and are frequently inserted under poor aseptic conditions (6).

The CDC have addressed this issue initially by recommending that all cannulae inserted in emergency situations must be removed or changed on hospital wards within the first 48 h of admission and every 72 h irrespective of the presence of infection. Ward nurses were, however, highly reluctant to change recently inserted vascular catheters. Furthermore, other studies have been unable to demonstrate an increased risk of complications after three days of peripheral vascular catheterisation and have questioned the CDC recommendation for the routine replacement of cannulae (12, 13). Cannulae used in paediatric patients may remain in place as long as needed, provided sites remain free of complications (category IB). Although peripheral cannulae insertion isn’t a sterile procedure, it requires the use of aseptic, no-touch procedure (14).

Major cannula manufacturers are aggressively marketing their "Safety Cannula" claiming needle stick injury is a major occupational hazard. 196-2004, the number of staff exposed to injuries sustained from sharp instruments were published by occupational disease surveillance in UK. 997 were exposed to Hepatitis C, 551 to HIV and 181 to Hepatitis B. The number of staff contracting infections were 9 Hep C (Risk 1 in 3), Hep B (Risk 1 in 30) and HIV (Risk 1 in 300). Comparing this with the risk of contracting and infecting patients with antibiotic resistant bacterial infection is very high. Nearly 18,650 people died from MRSA infection and 94,000 others were seriously sickened in 2005, according to the Centres for Disease Control and Prevention.

As house officers claim the success of inserting cannulae in the first attempt is about 60% and rate improved to 90% as seniors doctor (7). Multiple attempts to introduce cannula are traumatic and increase the incidence of introducing infections because adequate skin preparation is not often good in subsequent attempts. Biocides, used in hospitals to decontaminate skin before practical procedure if weak allow the bacteria to survive and grow stronger. This new development is bad news for hospital staff and patients.

Since twenty years both communities acquired and hospital-acquired staphylococcal infections increased and this trend parallels the increased use of intravascular device. Vascular access development and the frequency of used technique to save life are now threatening mankind.

Trend of Staphylococcus infections parallels the increased use of intravascular device

12. Kelli R, Pinpointing intravascular device infections; Nursing Management (Springhouse): Volume 34(6) June 2003pp 35-42.

13. Mimoz O, Pieroni I, Lawrence C, et al. Prospective randomized trial of two antiseptic solutions for preventing CV or arterial colonization and infection in intensive care unit patients. Crit Care Med. 1996; 24: 1818-18

20. R.J. Pratta*, C.M. Pellowea, J.A. Wilsona,b, H.P. Lovedaya, P.J. Harpera, S.R.L.J. Jonesa, C. McDougallb, M.H. Wilcoxc; National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England; Journal of Hospital Infection (2007) 65S, S1–S64; http://www.epic.tvu.ac.uk/PDF%20Files/epic2/epic2-final.pdf