Advertisement
Bethyl Laboratories
Bethyl Laboratories

Opinion: 5 ways to save antibiotics

Here's what we need to do to create new antibiotics and extend the life of those that already exist

By | December 14, 2010

The world is linkurl:facing a crisis:;http://www.the-scientist.com/news/display/55951/ Bacteria have become linkurl:more and more resistant;http://www.the-scientist.com/news/display/53982/ to virtually all existing antibiotics, yet many companies are abandoning the field in favor of more lucrative medicines.
Ron Najafi
Image: NovaBay
People are proposing various solutions, such as offering financial incentives to the pharmaceutical industry to linkurl:spur the development of vitally needed antibiotics.;http://www.the-scientist.com/article/display/57352/ But along with creating new drugs, we can get more life from our existing antibiotics and maintain their utility. As the head of a company focused on the development of compounds to treat and prevent a wide range of infections without causing bacterial resistance, this is an issue I find both fascinating and vitally important. In my opinion, there are five ways we can extend the functional life of our antibiotic arsenal. 1. Do the obvious In a recent linkurl:New York Times;http://www.nytimes.com/2010/11/06/health/policy/06germ.html article, linkurl:Ramanan Laxminarayan,;http://www.rff.org/Researchers/Pages/ResearchersBio.aspx?ResearcherID=41 director of the linkurl:Extending the Cure;http://www.extendingthecure.org/ project on antibiotic resistance at the policy organization linkurl:Resources for the Future,;http://www.rff.org/Pages/default.aspx suggested that the government should focus on conserving the effectiveness of existing antibiotics by preventing their unnecessary use in people and farm animals, and by requiring better infection control measures in hospitals. These are crucial steps, which should be taken immediately. First, we must stop and assess the use of antibiotics as additives to the feed of our farm animals, and specifically prevent the unnecessary use of antibiotics in animals that are not sick. The U.S. Congress has already urged farmers to stop the overuse of antibiotics in animals because it is creating new, drug-resistant strains of bacteria that can spread to humans. A recent linkurl:CBS news report spotlighted microbiologist Stuart Levy;http://www.cbsnews.com/stories/2010/07/16/eveningnews/main6685734.shtml at Tufts University, the individual who identified tetracycline resistance in chickens more than 30 years ago. In his research, nearly all of the E. coli in the intestinal tracts of the chickens become tetracycline-resistant after one week of treatment. 2. Assess the impact Sub-lethal quantities of antibiotics are known to create an environment for the development of resistance and multi-drug resistance mechanisms. We need to monitor the fate of all the mega-quantities of antibiotics sold as prescriptions and as over-the-counter medicine: Do they end up in our wastewater systems and landfills and become a breeding ground for new superbugs? What happens to the groundwater runoff from farms, sewage systems, and landfills?
NovaBay scientist at work
Image: NovaBay
3. Explore entirely different drugs We must look for antibiotics utilizing new mechanisms without the development of resistance. Simply adding new drugs to existing classes isn't cutting it. My company is developing a new class of agents with a novel mechanism of action that kills pathogens without the potential for resistance. These are fast acting, broad-spectrum, multi-targeting agents that do not persist in the environment. Confirmatory experiments in our labs are slated for publication in 2011. The preliminary experiments indicate that our linkurl:Aganocide compounds;http://www.novabaypharma.com/investors/release/Oct_25_2010_Impetigo_trial exert their activity against pathogens by the rapid and preferential inactivation of specific amino acid residues on essential membrane proteins, such as ATP machinery or ion channels which are located on the membrane of the bacteria. However, this machinery is protected inside of the mammalian cells. The consequence of this inactivation induces a change in the protein's tertiary structures and results in dysfunction, dysregulation or protein shedding from the membranes of pathogens. The end result is a fast-acting, broad-spectrum antimicrobial agent that is safe to mammalian cells within a therapeutics window. We continue to confirm these findings and integrate these observations into the elucidation of the mechanism of action as we develop this new class of antimicrobial agents. 4. Inactivate multiple essential targets When we attack bacteria with agents targeted against one particular cellular mechanism -- for example, fluoroquinolones target DNA gyrase -- the bugs simply select for a mutation to that mechanism that make them resistant, and the agent becomes ineffective. This will always be true of targeted agents, so we wind up with more of these agents every few years. We urgently need a parallel initiative in the development of multi-target agents, such as non-antibiotic agents that can inactivate essential protein targets that mutations cannot sidestep, and are not damaging to human tissues. As stated above, our company is currently pursuing multi-target agents. Subtle and selective multi-target agents to which bacteria cannot develop mutational resistance are the key to solving this huge problem. They are pivotal for our survival and should have fast-track consideration by all agencies. 5. Encourage and incentivize the industry Finally, we should encourage and incentivize the pharmaceutical and biotech industry to develop safe and effective non-antibiotic anti-infectives that could replace all topical antibiotics for eyes, skin, ear, over-the-counter antibiotics, etc. Overall, we need to understand the sources of antibiotic resistance -- whether it originates in farms, sewers, landfills, or other locations -- and find ways to save our precious few antibiotics for systemic blood-borne infections. Otherwise, the overall result will be fewer effective drugs to treat bad bugs. Ron Najafi, PhD is chairman and CEO of linkurl:NovaBay Pharmaceuticals, Inc (NBY).,;http://www.novabaypharma.com/company/profile an Emeryville, California-based biotechnology company developing anti-infective compounds for the treatment and prevention of antibiotic-resistant infections. He can be reached at rnajafi@novabaypharma.com.
**__Related stories:__***linkurl:MRSA: RIP?;http://www.the-scientist.com/news/display/53982/
[11th December 2007] *linkurl:Rising plague;http://www.the-scientist.com/news/display/55951/
[27th August 2009] *linkurl:Garden of antimicrobial delights;http://www.the-scientist.com/article/display/57352/
[May 2010]
Advertisement
The Scientist
The Scientist

Comments

Avatar of: anonymous poster

anonymous poster

Posts: 1

December 14, 2010

Seems like a major issue is this focus on raging ''war'' against invading organisms (which obviously will fight back). This is natural considering that this type of medicine is essentially an extension of what our body tends to do during infections.\n\nI'm curious, have there been other avenues explored for treatments? Rather then focusing on eradicating invading organisms, is there research or evidence outhere looking at strategies for enhancing ''containement'' of invasions until the body either a) safely takes care of it or b) ''allows'' the organisms to run their own life-course? \n\nAppologies for such a naive question, only curious to know if there are innovative or ''outside the box'' models already outhere.
Avatar of: john toeppen

john toeppen

Posts: 52

December 14, 2010

The use of corn as a feed for cattle causes them to become ill since they are ?designed? to eat forage materials. Antibiotics are used to mitigate the problems caused by using the wrong feed. However, corn is a major business as is beef, and these economics apparently carry more weight than the health of our population.\n\nAlgae is suitable as a cattle feed as it can be 40% oil by weight and can be grown to double its weight every day. Algae thrives on the nutrients available in waste water and is easily farmed. Carbon dioxide is available in abundance (a single coal burning power plant uses 200 train cars of coal a day which would be about 800 cars of dry ice if captured). Algae economics look much better if it is used to capture CO2, used to feed cattle, used to clean water, and used as a biofuel.\n
Avatar of: anonymous poster

anonymous poster

Posts: 1

December 14, 2010

Whatever happened to the lytic viruses that the Soviet bloc used as an alternative to antibiotics. If there really was something to them surely we are now closer to being able to understand how to use them safely?
Avatar of: Colin Higgins

Colin Higgins

Posts: 1

December 14, 2010

If inhibiting a protein causes lethality in a population, you are applying selection. No matter how efficacious your agent, mutations conveying resistance to your drug will arise at a statistically determined rate. Your resistance-resistant novel drug class would controvert the theory of natural selection. A weighty claim, and one that I think will ultimately fail the test of experiment.\n\nCombination therapy has been shown to be remarkably effective in anti-HIV cocktails, and it seems to be the way to go. Deliver antibiotics targeted to ten different targets, and require the bugs to undergo 10 simultaneous mutations.
Avatar of: Mike Waldrep

Mike Waldrep

Posts: 155

December 14, 2010

Interesting!

December 14, 2010

Ron Najafi wrote:\n"...to develop safe and effective non-antibiotic anti-infectives that could replace all topical antibiotics for eyes, skin, ear, over-the-counter antibiotics..."\n\nWell, they are developed already - they are called "antiseptics", some of them known, perhaps, even before Hippocrates ;-) \nSome of them do not promote bacteria to evolve resistance, but some other do. \nHowever, the problem with topical antiseptic formulations is - that they are too cheap... \nThus, the manufacturer (and the pharmacist too) will rather promote and advertise quite elaborated and expensive "triple protection antibiotic with anesthetic" ointment, than let's say a cheap "Camphor-phenol" formulation (phenol has been used since times of Ignaz Semmelweis without producing resistant strains)...\n
Avatar of: KEVIN HEALEY

KEVIN HEALEY

Posts: 2

December 14, 2010

As indicated by "Anonymous", bacteriophage have an important role to play in treating / preventing disease related to bacterial infections. Numerous research projects are underway by reputable organisations, including VetPhage in Australia for animal health applications.
Avatar of: anonymous poster

anonymous poster

Posts: 107

December 14, 2010

A not-very-subtle plug for the author's commercial interests. Should have been clearly labeled "Advertising".
Avatar of: Edo McGowan

Edo McGowan

Posts: 19

December 14, 2010

Some thoughts on ways to extend the life of antibiotics. One way is to reduce the number of antibiotic resistant microbes that are released to the environment. Accordingly, it will be necessary to control the release of resistant pathogens that is occurring in American rivers and on our farmlands through wastewater processing and thus sewage and its byproducts. These byproducts include reclaimed (recycled) water, sewage sludge (biosolids) and composted biosolids. \n\nWe are seeing that the FDA is active in reviewing antimicrobials used in agriculture and that is one control mechanism. In a message (Government Agencies FDA Releases First Estimate on Antibiotics in Ag by Helena Bottemiller | Dec 13, 2010), as forwarded by ROAR discusses this FDA activity. \n\nAllow me thus to explore another route where the expansion of resistance in the environment could be greatly reduced but where the requisite federal and state agencies that one might think should be involved are tactfully absent.\n\nWe here in Santa Barbara are working on resistance as found within sewage and spread by sewage and its byproducts. Although having funded a major study on wastewater generated antibiotic resistance in the late 1970s, see: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC241834/pdf/aem00183-0119.pdf, the US/EPA has remained silent on the topic. Its higher management assures me that it has none of its scientist working on the topic. Since the paper by the Wastewater Research Division, Municipal Environmental Research Laboratory, U.S. Environmental Protection Agency, Cincinnati, Ohio came out in 1981, the agency has seen fit to pull the entire study and its background data from the entire EPA website and data base. One might ask, why? Interestingly the material is also absent from the data base of the CDC. I also brought up this study and the topic of wastewater created antibiotic resistant microbes with the CDC and all they could tell me about it was that CDC had no focus on the topic. I then went to the federal Inter Agency Task Force on Antibiotic Resistance, asking them where they were on the topic---answer, not part of their focus.\n\nWe are in a conversation with the State of California on this topic. The state is attempting to ignore the topic. We have informed the state that in our testing reclaimed water that is state certified and used on crops consumed raw, we find multi-antibiotic resistant bacteria in the same groupings containing serious pathogens. We have suggested that the state repeat our work, but that suggestion falls on deaf ears. In using the state approved lab tests for this water, when we test the reclaimed (recycled) water just as it leaves the treatment works we often get non-detect. But when we test it down the pipe at point of use we often find it wildly outside allowed limits. Thus something is happening during the transit to the sprinkler. We suspect that it is either development of biofilms from the bacteria in the reclaimed water and the fact that it is quite nutrient rich. Another possibility is that bacteria are in the viable but non-culturable state (VBNC) and resuscitate while in transit. It could also be a combination of these two processes. The up-shot is that bacteria bearing antibiotic resistance are being put on crops consumed raw and these bacteria can be internalized in the crop where no amount of washing at the kitchen sink will have any effect. Once these bacteria are in the human gut they can multiply.\n\nHere is a bit from the 1981 work by US/EPA:\n\n"Several researchers have pointed out that\nwastewater, treated or untreated, is a primary\ncontributor of bacteria to the aquatic ecosystem\n(12, 16, 17, 20, 27, 29). Studies have been\nconducted which demonstrate that significant\nnumbers of multiple drug-resistant coliforms occur\nin rivers (17), bays (9), bathing beaches (28),\nand coastal canals (13). Waters contaminated by\nbacteria capable of transferring drug resistance\nare of great concern since there is the potential\nfor transfer of antibiotic resistance to a pathogenic\nspecies."\n\n"When bacteria which carry transmissible Rfactors\n(R+ bacteria) are ingested by a human\nhost, the R-factors may transfer into commonly\noccurring bacteria of the gastrointestinal tract\n(32). These organisms may subsequently transfer\nthis resistance to pathogenic organisms, resulting\nin reduced efficacy of antimicrobial chemotherapy\nin the event of an infection. In vivo\nstudies have shown that when individuals carrying\nR+ bacteria are subjected to antibiotic therapy, these organisms flourish and transfer their\nresistance to other bacteria (25)."\n\n\nThese bacteria when released by sewage treatment or contained within sewage byproducts are thus able to colonize environmental niches, and animals, including humans, through ingestion. Once ingested, the plasmids may be transferred to normal flora, and subsequently to pathogenic bacteria found in humans or animals, making later treatment with particular antibiotics ineffective. Also one must consider transfer of genetic information from these organisms to more robust organisms as highlighted by Sjolund et al. (2005) [1] indicating that resistance in the normal flora, which may last for several years, might contribute to increased resistance in higher-grade pathogens through interspecies transfer.\n\nSjolund et al go on to note that since populations of the normal biota are large, this affords the chance for multiple and different resistant variants to develop. This thus enhances the risk for spread to populations of pathogens. Furthermore, there is crossed resistance. For example, vancomycin resistance may be maintained by using macrolides [2]. Sjolund also notes that the resultant effects from these gene transfers can remain within the gut biota for years.\n\nSchentag, et al. (2003), as found in Walsh [3], followed surgical patients with the subsequent results. Pre-op nasal cultures found Staphylococcus aureus 100% antibiotic susceptible. Pre-op prophylactic antibiotics were administered. Following surgery, cephalosporin was administered. Ninety percent of the patients went home at post-op day 2 without infectious complications. Nasal bacteria counts on these patients had dropped from 10/5th to 10/3rd, but were now a mix of sensitive, borderline, and resistant Staphylococcus sp. By comparison, prior to surgery, all of the patients? Staphylococcus samples had been susceptible to antibiotics. For the patients remaining in the hospital and who were switched on post-op day 5 to a second generation cephalosporin (ceftazidine), showed bacterial counts up 1000-fold when assayed on post-op day 7 and most of these were methicillin resistant Staphylococcus aureus (MRSA). These patients were switched to a 2-week course of vancomycin. Cultures from those remaining in the hospital on day 21, revealed vancomycin resistant enterococcus (VRE) and candida. Vancomycin resistant enterococci infections can produce mortality rates of between 42 and 81%.\n\n\nNote in the above, that these patients in the Schentag study harbored NO resistant bacteria in their nasal cavities upon entry to the hospital. But what would be the result if there had been inadvertent acquisition of resistance from environmental contamination such as through sewage sludge or recycled water\n\nThis then brings into question the current paradigm on infection and its dose response to a certain load of a particular pathogen, i.e., ID and LD 50s. Lateral transfer of mobile genetic elements conferring resistance is not considered in this old paradigm. With the prodigious capacity for the gut bacteria to multiply, once the lateral transfer has taken place, very small original numbers---well below the old paradigms can be multiplied into impressive numbers. Since viruses and phages are also involved, their capacity to multiply, which dwarfs that of bacteria, must also be included. Thus there is a need for a new paradigm; unfortunately, the regulatory community seems not to recognize this. When one considers the multiplication within sewer plants and also within their byproducts, disbursement into the environment, the transfer to background organisms, hence to man and his animals, then the remultiplication within commensals, the emerging picture is worrisome.\n\nFurther, there are opportunities and interrelationships between microbes that can degrade antibiotics, eg. antibiotic resistant bacteria, and those that can degrade metals as well as pesticides and farm chemicals that are already found in agricultural soils. In many cases, the involved cellular machinery is the same or similar, i.e., a duality (see Schlüter and abstracts of others below). Thus, in placing sewage sludge (biosolids) on agricultural land one is introducing serious human pathogens into an already primed environment, one in which food crops are grown or pasture is maintained.\n\nThis duality may have some interesting synergistic survival advantages for the microbes, but bad-for-human-health effects when considering sewer sludge as applied to heavily farmed lands.\n\nThe current standards controlling sewer plant operations, production of reclaimed water, the land application of sewer sludge (biosolids) or the composting of sewer sludge for making compost and potting soils consider none of these issues.\n\nDr Edo McGowan\n\nReferenced Material\n\n\n[1] Sjolund et al. (2005) Emerging Infectious Diseases (Vol. 11, # 9, Sept 2005 @ p. 1389 et seq)\n\n\n[2] Giacometti A, Cirioni O, Kamysz W, Silvestri C, Licci A, D'Amato G, Nadolski P, Riva A, Lukasiak J, Scalise G. In vitro activity and killing effect of uperin 3.6 against gram- positive cocci isolated from immunocompromised patients. Antimicrob Agents Chemother. 2005 Sep;49(9):3933-6. Robertson GT, Zhao J, Desai BV, Coleman WH, Nicas TI, Gilmour R, Grinius L, Morrison DA, Winkler ME. Vancomycin tolerance induced by erythromycin but not by loss of vncRS, vex3, or pep27 function in Streptococcus pneumoniae. J Bacteriol. 2002 Dec;184(24):6987-7000. ].\n\n[3] Walsch, C. Antibiotics----, Actions, Origins, Resistance, (March 2003) New York: ASM Press.\n\n\nThe 64 508 bp IncP-1 antibiotic multiresistance plasmid pB10 isolated from a waste-water treatment plant provides evidence for recombination between members of different branches of the IncP-1 group\nA. Schlüter, et al\nThe complete 64 508 bp nucleotide sequence of the IncP-1 antibiotic-resistance plasmid pB10, which was isolated from a waste-water treatment plant in Germany and mediates resistance against the antimicrobial agents amoxicillin, streptomycin, sulfonamides and tetracycline and against mercury ions, was determined and analysed. A typical class 1 integron with completely conserved 5' and 3' segments is inserted between the tra and trb regions. The two mobile gene cassettes of this integron encode a -lactamase of the oxacillin-hydrolysing type (Oxa-2) and a gene product of unknown function (OrfE-like), respectively. The pB10-specific gene load present between the replication module (trfA1) and the origin of vegetative replication (oriV) is composed of four class II (Tn3 family) transposable elements: (i) a Tn501-like mercury-resistance (mer) transposon downstream of the trfA1 gene, (ii) a truncated derivative of the widespread streptomycin-resistance transposon Tn5393c, (iii) the insertion sequence element IS1071 and (iv) a Tn1721-like transposon that contains the tetracycline-resistance genes tetA and tetR. A very similar Tn501-like mer transposon is present in the same target site of the IncP-1 degradative plasmid pJP4 and the IncP-1 resistance plasmid R906, suggesting that pB10, R906 and pJP4 are derivatives of a common ancestor. Interestingly, large parts of the predicted pB10 restriction map, except for the tetracycline-resistance determinant, are identical to that of R906. It thus appears that plasmid pB10 acquired as many as five resistance genes via three transposons and one integron, which it may rapidly spread among bacterial populations given its high promiscuity??.\n-----------------------------------\nValidity of the Indicator Organism Paradigm for Pathogen Reduction in Reclaimed Water and Public Health Protection.\n\nValerie J. Harwood\n\n \nReceived 27 September 2004/ Accepted 20 December 2004\n\nThe validity of using indicator organisms (total and fecal coliforms, enterococci, Clostridium perfringens, and F-specific coliphages) to predict the presence or absence of pathogens (infectious enteric viruses, Cryptosporidium, and Giardia) was tested at six wastewater reclamation facilities. Multiple samplings conducted at each facility over a 1-year period. Larger sample volumes for indicators (0.2 to 0.4 liters) and pathogens (30 to 100 liters) resulted in more sensitive detection limits than are typical of routine monitoring. Microorganisms were detected in disinfected effluent samples at the following frequencies: total coliforms, 63%; fecal coliforms, 27%; enterococci, 27%; C. perfringens, 61%; F-specific coliphages, ~40%; and enteric viruses, 31%. Cryptosporidium oocysts and Giardia cysts were detected in 70% and 80%, respectively, of reclaimed water samples. Viable Cryptosporidium, based on cell culture infectivity assays, was detected in 20% of the reclaimed water samples. No strong correlation was found for any indicator-pathogen combination. When data for all indicators were tested using discriminant analysis, the presence/absence patterns for Giardia cysts, Cryptosporidium oocysts, infectious Cryptosporidium, and infectious enteric viruses were predicted for over 71% of disinfected effluents. The failure of measurements of single indicator organism to correlate with pathogens suggests that public health is not adequately protected by simple monitoring schemes based on detection of a single indicator, particularly at the detection limits routinely employed. Monitoring a suite of indicator organisms in reclaimed effluent is more likely to be predictive of the presence of certain pathogens, and a need for additional pathogen monitoring in reclaimed water in order to protect public health is suggested by this study.\n
Avatar of: Graham Small

Graham Small

Posts: 6

December 15, 2010

Similar problems are encountered with multiple resistance to pesticides in arthropod pests of agricultural, veterinary and public health importance. Therefore, resistance management strategies have been implemented, some of which may be of use in managing antibiotic resistance:\n(1) Only prescribe antibiotics when its absolutely required;\n(2) Implement a rotation of prescribed antibiotics with different modes of action to reduce the selection pressure on antibiotic classes;\n(3) Combine antibiotics with different modes of action into a single formulation.\n
Avatar of: anonymous poster

anonymous poster

Posts: 13

December 16, 2010

Prior to the advent of antibiotics, the outcome of infections running their natural courses was a lot of dead people.\nAnd, I object to the various statements that imply that bacteria are somehow striving to develop resistance. Rather, selection is imposed on a population ALREADY harboring mutations that will confer resistance. Inappropriate prescription and incorrect usage provide selection scenarios that eventually yield additional resistant strains. And bacteria are very good at sharing those factors via plasmid exchange, etc.\nThe article struck me as a fund-raising pitch for the author's company.
Avatar of: Philip Onigman

Philip Onigman

Posts: 1

December 17, 2010

Hospitals use significant quantities of antibiotics for "coverage" of infection, when a clinician starts an antimicrobial agent based on either early symptoms of possible infection (fever) or early diagnostic indicators of infection (positive blood culture).\n\nThis practice can be fine-tuned now, because more rapid species identification methods are now available. Vancomycin is one of the most widely used antibiotics in hospitals. Vancomycin can induce its own resistance during and requires ever higher earlier doses in order to fight Staphylococcus aureus bloodstream infections. For decades, vancomyicn was been prescribed 1-2 grams per day (weight adjusted) for the first several days on the signal of a positive blood culture that is considered "Gram positive". IDSA guidelines now call for consideration of nearly doubling the daily dose of vanmcomycin in order to be effective. Unfortunately for many patients, higher vancomycin doses have toxic effects (kidney function). This dilemma adds additional costs of serum drug level monitoring and more careful calculations of drug dosing. (Am J Health-Syst Pharm 2009 v.66 p.82-98). The increased management requirements of vancomycin dosing are also driving faster utilization of several drugs such as daptomycin, linezolid or tigecycline that could be held in reserve.\n\nHowever, at most hospitals, 60-70% of "Gram positive cocci in clusters" (GPCC) primary blood culture reports ultimately prove to be coagulase negative staph (CNS), that are skin colonizers. When the bottle grows CNS, the initial Lab report of GPCC can trigger an unnecessary 3-5 days of IV vancomycin therapy for an inpatient that does not have a bloodstream infection. Depending on the dosing of vancomycin in early stages, if the clinician is unsure of infection vs contamination, the vancomycin could be under-dosed or entirely unnecessary. Exceptions are cases of CNS Lab data and patient symptoms and history that warrant continuation of antibiotics to treat infections caused by coagulase negative staph.\n\nForrest, et al (JAC 2006 v.58 no.1 p. 154-8) first described the practice of proactively limiting vancomycin for CNS to either a single initial dose, or avoidance of vancomycin altogether vs the usual 6-10 grams that would otherwise be administered over 3-5 days. This report also concluded that shorter courses of unnecessary vancomycin enabled their hospital to safely shorten length of hospitalization for many patients.\n\nLy, et al (Therapeutic Clinical Risk Management 2008 v.4 no.3 p.637-40) found that rapid identification with very effective notification of infection vs contamination and educational support to attending clinicians resulted not only in reduction of unnecessary antibiotics and shorter hospitalizations, but a reduced mortality for ICU cases becasue the message of "infection" from the Lab triggered an earlier, certain and more aggressive course of antibiotics; therefore effective and appropriate use.\n\nThe old paradigm is "It is safe to use antibiotics for several days to cover in case of serious infection while we wait for complete diagnostics".\n\nThe new paradigm is "We have rapid species identification and decision support that rules in or rules out a serious pathogen. When patient symptoms and chart indicate no infection, we can discontinue coverage antibiotics sooner".\n\n
Avatar of: sidney kurn

sidney kurn

Posts: 2

December 26, 2010

Mr. Higgins raises an interesting point regarding natural selection. Let us assume that the unit of selection is the gene, and the rate of evolution of the phenotype of the bacteria depends upon the interaction of environmental selection with the rate of favorable and unfavorable gene mutations. The time for successful adaptation of the bacteria would be proportional to the number of molecules oxidized by the chlorotaurine antimicrobial. It is my understanding that many sites on a myriad of molecules are affected. The time to successful adaptation would appear to be many times longer than the time to develop resistance to conventional antibiotics, which generally effect a single enzyme or molecular process. In fact, the use of chlorinated compounds, over the last 180 years has not resulted in bacterial resistance. In addition, chlorotaurines, from an evolutionary standpoint, have been a very stable cellular mechanism for bactericidal activity, presumably for a very long time.
Avatar of: sidney kurn

sidney kurn

Posts: 2

December 26, 2010

Mr. Higgins raises an interesting point regarding natural selection. Let us assume that the unit of selection is the gene, and the rate of evolution of the phenotype of the bacteria depends upon the interaction of environmental selection with the rate of favorable and unfavorable gene mutations. The time for successful adaptation of the bacteria would be proportional to the number of molecules oxidized by the chlorotaurine antimicrobial. It is my understanding that many sites on a myriad of molecules are affected. The time to successful adaptation would appear to be many times longer than the time to develop resistance to conventional antibiotics, which generally effect a single enzyme or molecular process. In fact, the use of chlorinated compounds, over the last 180 years has not resulted in bacterial resistance. In addition, chlorotaurines, from an evolutionary standpoint, have been a very stable cellular mechanism for bactericidal activity, presumably for a very long time.

Follow The Scientist

icon-facebook icon-linkedin icon-twitter icon-vimeo icon-youtube

Stay Connected with The Scientist

  • icon-facebook The Scientist Magazine
  • icon-facebook The Scientist Careers
  • icon-facebook Neuroscience Research Techniques
  • icon-facebook Genetic Research Techniques
  • icon-facebook Cell Culture Techniques
  • icon-facebook Microbiology and Immunology
  • icon-facebook Cancer Research and Technology
  • icon-facebook Stem Cell and Regenerative Science
Advertisement
Advertisement
Life Technologies