A few weeks ago the American Center for Disease Control and Prevention (CDC) published the Threat Report 2013 which “for the first time ever maps the load and threat of antibiotic-resistant germs and their effects on human health”. CDC Director Tom Peace outlined the situation with haunting words: “If we are not careful, the medicine cabinet will be empty at a time when doctors will need resources for treatment”. They would be missing the antibiotics which they need for saving lives.
The 2012-published ALERTS study calculated a five percent probability of any clinic patient getting infected by a typical hospital bacteria. One in fifty of these patients die from it. Over a hundred thousand times a year with such events, it’s MRSA – methicillin-resistant Staphylococcus aureus – germs which strike, something against which a variety of previously successful antibiotics no longer measure up today. A few months ago the German medical journal Ärzteblatt reported on the first VRSA case in Europe. In this case the Staphylococci cells had in addition gained resistance to vancomycin, a feature that almost gives them the status of invulnerability.
Compared to the constant increases in infections involving resistant organisms, the amount of development in the area of new antibiotics is very sparse. In the eighties, almost thirty new antibacterial agents entered the market, since 2000 the number of such new entries totals nine.
Problem case CA-MRSA
Increased awareness of hygiene and strict measures in clinics and hospitals, which are aimed at preventing the spread of dangerous germs, have at least strongly flattened the steep statistical curve describing the occurrence of these clinic-based infections. In contrast however, the threat now reappears elsewhere in a different form. Little studied as yet are bacterial strains that are just as resistant to multiple antibiotics as those dreaded ones in the clinic, but cause problems in the domestic home zone. Those infected in these instances mostly have no history of medical treatment in the clinic or doctor’s office, have had no contact with antibiotics for a long time and do not suffer from a chronic illness or age-related weakness of the immune system.
These so-called CA-MRSA (community-associated MRSA) are clearly different with respect to their genetic material from typical hospital germs. In Germany they are still relatively rare – but probably statistically associated with a high number of unreported cases. Often involving familial clustering they occasionally result in long-term recurrent progress of disease. According to numbers derived by Roger Stephen of the University of Zurich, multi-resistant pathogens find a home in every sixth healthy person.
Stock exchange for resistance genes
The household is therefore also a hub for resistance factors in bacteria. Other staphylococci (such as St. pseudo intermedicus, St. schleiferi), but also other bacterial genera such as Enterococci can operate a useful gene exchange system which benefits Staphylococcus aureus. In contrast to the hospital, in the home few potential bacterial hosts are in intensive contact with one another, instead usually having contact over an extended time period. Depending on the environment germs have it easier dealing with hygiene that is not so intense, even surviving for three months or more in the kitchen cabinet.
In Germany in 35 percent of all households a cat or dog is also one of the cohabitants. They are vectors as well. In the journal PloSOne, Birgit Walther and her colleagues from the University of Berlin report on studies made of a dog show in 2009. Smears from nearly twenty percent of dog owners and two percent of their four-legged friends were found to contain Staphylococcus aureus germs. Staphylococcus intermedicus turned up in samples from fourteen percent of dogs and six percent of their holders. Almost half of these isolates were resistant to more than one antibiotic. Almost all dogs were occasionally able to lick the hands of their human room mates – creating a light transmission path for the microbes in both directions. Clinical MRSA strains are also found in parrots, rabbits, hamsters, guinea pigs and turtles.
Long term carriers
Depending on the study, the transmission rates of germs from those infected to the other members of their household amount to 10-43 percent. This calculation essentially depends on the number of household members, their living standard and the bacterial strain itself. Every fifth MRSA carrier provides his or her MRSA colony with a home for many months or even years. Thus he or she can also repeatedly reinfect family members who have since gotten rid of the germs.
Those who want to study the distribution of “household staphylococci” should not limit themselves to looking at nasal swabs. The throat, skin, perineum and clinical lesions are also popular accommodation places for them. Studies have shown that the nasal swab alone reveals only about half of the infected household members. The same holds true for four-legged members of the household.
Infected animal herds
MRSA strains that have only just made themselves cozily at home in the host are not totally easy to get rid of again. Detergent alone is often not enough, for instance, to make dishes staphylococcus free. Mexican researchers as part of an article in the Journal of Applied Microbiology recommend a two percent hypochlorite solution or detergent with a chlorine/ammonia combination. General hygiene in the home is however also important, such as regular changing of linen and the strict separation of sleeping and resting places of pets and humans. For most pets, human MRSA bacteria are not pathogenic and are eliminated by their own immune system. Good studies on effective disinfection of domestic animals however barely exist.
68 percent of poultry flocks and 14 percent of ruminants and pigs carry colonies of multi-resistant germs, states Robert Stephan reporting on the situation in Switzerland. According to data from the Robert Koch Institute, LA (livestock associated)-MRSA infections of humans who are employed in animal fattening are (still) rare and with very few exceptions have no serious clinical course of progress. Nevertheless, there exists the risk of further transmission of resistance factors to other bacteria and within the human body.
Most concerns held by the health authorities in recent times relate to the spread of enterobacteria such as Klebsiella strains which are resistant to carbapenems. Carbapenems are “reserve antibiotics” and are often considered the “last resort” in the instance of an infection which is no longer containable using other antimicrobial agents.
Very often out of economic considerations, many companies discontinue development projects for new antibiotics. In order to get rid of multi drug-resistant bacteria, strict hygiene rules and regular tests for bacterial colonisation in the clinic and in the household are therefore probably of most help.
Collateral Sensitivity Cycling
A small glimmer of hope is conveyed in at least one article which appeared in recent days in Science Translational Medicine. At least in the lab a strategy of “collateral sensitivity cycling” is working with E.coli. The Danish authors exploited the characteristic of the bacteria to lose an older resistance alongside the acquisition of a new resistance and to thus again become sensitive to certain antibiotics. Using this “to-and-fro swinging” between two sets of antibiotics, we could manage in this way to also out-trick multi-resistant organisms. There would at least be a possibility, worthy of being tested out here, of one day not being confronted despairingly by infections arising because pathogenic bacteria have learned to eliminate all of our weapons.