Wednesday, February 29, 2012

New method gives access to treasure trove of potential new antibiotics

New method gives access to treasure trove of potential new antibiotics


Scientists are reporting use of a new technology for sifting through the world's largest remaining pool of potential antibiotics to discover two new antibiotics that work against deadly resistant microbes, including the "super bugs" known as MRSA. Their report appears in the Journal of the American Chemical Society.

Sean Brady and colleagues explain that an urgent need exists for new medications to cope with microbes that shrug off the most powerful traditional antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) infections, for instance, are resistant to most known antibiotics. MRSA strikes at least 280,000 people in the U.S. alone every year, and almost 20,000 of those patients die. The typical way of discovering new antibiotics involves identifying and growing new bacteria from soil and other environmental samples in culture dishes in the laboratory. That environmental treasure-trove is the largest remaining potential source of new antibiotics. Researchers then analyse the bacteria to see if they make substances that could be used as antibiotics to kill other microbes. But most bacteria found in nature can't grow in the laboratory. That's why Brady and colleagues took a new approach to this problem.

The researchers removed DNA from soil bacteria that wouldn't grow in the lab. Then, they put this DNA into different bacteria that do grow well in culture dishes, and these bacteria acted like incubators for the new DNA. The approach enabled Brady's team to study the substances made by the soil bacteria's DNA in the lab. With this "metagenomics" method, they identified two new possible antibiotics called fasamycin A and fasamycin B that killed MRSA and vancomycin-resistant Enterococcus faecalis, which also is becoming more resistant to known antibiotics. They also determined how the new antibiotics work. "Metagenomics has the potential to access large numbers of previously inaccessible natural antibiotics," say the researchers.

Virtual Medicine

Sunday, February 26, 2012

Reasons for inappropriate prescribing of antibiotics in a high-complexity pediatric hospital

Reasons for inappropriate prescribing of antibiotics in a high-complexity pediatric hospital


Dec 2011

[Article in Spanish]

Abstract


OBJECTIVE:


Determine the reasons for inappropriate prescription of antibiotics and identify opportunities to improve prescription of these drugs in pediatric patients hospitalized in intermediate and intensive care units.


METHODS:


A prospective, descriptive longitudinal study was conducted of pediatric patients in intermediate and intensive care units who received parenteral administration of antibiotics, with the exception of newborns, burn unit patients, and surgical prophylaxis patients. A univariate analysis and multiple logistic regression were performed.


RESULTS:


A total of 376 patients with a median of age of 50 months were studied (interquartile range [IQR] 14.5-127 months). Out of the total patients studied, 75% had one or more underlying conditions. A total of 40.6% of these patients had an oncologic pathology and 33.5% had neurological conditions. The remaining 25.9% had other underlying conditions. Antibiotic treatment was inappropriate in 35.6% of the patients studied (N = 134). In 73 (54.4%) of the 134 cases, inappropriate use was due to the type of antibiotic prescribed, the dose administered, or the treatment period.


The 61 (45.5%) remaining cases did not require antibiotic treatment. In the multivariate analysis, the risk factors for inappropriate use of antibiotics were: administration of ceftriaxone OR 2 (95% CI, 1.3-3.7; P = 0.02); acute lower respiratory tract infection OR 1.8 (95% CI, 1.1-3.3; P < 0.04); onset of fever of unknown origin in hospital inpatients OR 5.55 (95% CI, 2.5-12; P < 0.0001); and febrile neutropenia OR 0.3 (95% CI, 0.1-0.7; P = 0.009).


CONCLUSIONS:

Inappropriate use of antibiotics was less common in the clinical conditions that were well-characterized. Prescribing practices that could be improved were identified through the preparation and circulation of guidelines for antibiotic use in hospital inpatients.


SciElo

Antibiotics production by an actinomycete isolated from the termite gut.

Antibiotics production by an actinomycete isolated from the termite gut.


Feb 2012

Source

Tropical Biosphere Research Center, University of the Ryukyus, Nishihara-cho, Okinawa, Japan. tmatsui@comb.u-ryukyu.ac.jp.

Abstract


As well as the search for new antibiotics, a new resource or strains for the known antibiotics is also important. Microbial symbionts in the gut of termites could be regarded as one of the feasible resource for such purpose. In this study, antibiotic-producing actinomycetes were screened from symbionts of the termite gut. 16SrRNA sequence analysis for the 10 isolates revealed that they belong to actinomycetes such as Streptomyces sp., Kitasatospora sp., and Mycobacterium sp. A culture broth from one of the isolate, namely strain CA1, belonging to the genera Streptomyces exhibited antagonistic activity against actinomycetes (Micrococcus spp.), gram-positive bacteria (Bacillus spp.), and yeast (Candida spp.). The structures of 2 compounds isolated from the culture broth of the strain CA1 were identified as those of actinomycin X2 and its analog, D. This study is the first to report that some symbionts of the termite gut are antibiotic-producing actinomycetes, and suggest that the termite gut is a feasible resource for bioprospecting.

Wiley OnLine


Promising antibiotic alternative to fight bacteria that causes strep throat

Promising antibiotic alternative to fight bacteria that causes strep throat


Feb 22, 2012

Researchers have discovered a promising alternative to common antibiotics used to fight the bacteria that causes strep throat. In an article published in the Proceedings of the National Academy of Sciences, the scientists discussed how their discovery could fight the infection with a reduced risk of antibiotic resistance.

By screening tens of thousands of small molecules, the team from the University of Missouri and University of Michigan identified a class of chemical compounds that significantly reduced the severity of group AStreptococcus (GAS) bacteria infection in mice. Their work suggests that the compounds might have therapeutic value in the treatment of strep and similar infections that affect an estimated 700 million people around the world each year. The newly identified compounds could work with conventional antibiotics, such as commonly prescribed penicillin, and result in more effective treatment.

"We know that 70 percent of bacteria causing infections in the hospital are resistant to at least one of the drugs commonly used for treatment," said Hongmin Sun, PhD, the article's first author and an assistant professor of internal medicine at the University of Missouri. "Rather than killing off the bacteria, this new compound changes the behavior of the bacteria and makes it less harmful."

Current antibiotics interfere with critical biological processes in the pathogen to kill it or stop its growth. But at the same time, stronger strains of harmful bacteria can sometimes resist the treatment and flourish.

"The widespread occurrence of antibiotic resistance among human pathogens is a major public health problem," said David Ginsburg, MD, a professor of internal medicine, human genetics, and pediatrics at the University of Michigan and a Howard Hughes Medical Institute investigator.

Source: University of Missouri School of Medicine

Chilean Avocado Could Combat Antibiotic-Resistant Bacteria, Study Suggests

Chilean Avocado Could Combat Antibiotic-Resistant Bacteria, Study Suggests

he Chilean avocado may have a role in the fight against antibiotic resistance, a new study suggests.

The research, published in the Journal of Microbial Chemotherapy shows that a substance in the Chilean avocado is able to hone in on a resistance mechanism ofStaphylococcus aureus (called yellow staphylococcus in the study and known commonly as 'staph infection'). This type of bacteria is the No. 1 cause of post-operation wound infection, and can also cause a variety of ills ranging from sepsis to food poisoning.

The avocado works in concert with traditional antibiotics to treat infections that are resistant to antibiotics alone. Researchers explained that a compound in the avocado is able to lower the "MIC level" of an antibiotic. The MIC Level is the lowest concentration of an antibiotic that is needed to stop the growth of bacteria. In this instance, the avocado compound lowered the antibiotic's MIC level by eight times.

Study researcher Jes Gitz Holler, of the University of Copenhagen, explained how the avocado assisted the antibiotic in a statement.

"Resistant bacteria have an efflux pump in their bacterial membrane that efficiently pumps out antibiotics as soon as they have gained access," Holler explained in the statement. "I have identified a natural substance that inhibits the pumping action, so that the bacteria's defense mechanisms are broken down and the antibiotic treatment allowed to work."

The leaves of this particular avocado plant are already used for wound healing among the Mapuche people in Chile, researchers explained.

Avocados aren't the only thing that have shown promise in the realm of infection-fighting. Scientific American reported on a study in the journal Microbiology showing that manuka honey -- honey made from the manuka flower -- is able to kill off strep bacteria in lab tests.


Huffington Post

Groups urge incentives for antibiotic research

Groups urge incentives for antibiotic research


February 24, 2012

By Jaimy Lee
Posted: February 24, 2012 - 12:00 pm ET

The Infectious Diseases Society of America and a coalition of groups representing patients, providers and others are advocating for the inclusion of economic incentives for antibiotic research and development in the reauthorization of the Prescription Drug User Fee Act.

The organizations said in a news release that they are contacting members of Congress about the need for economic incentives for the research and development of antibiotics, as well as diagnostic tests.

“The simple fact is we haven't found the right combination of incentives to convince pharmaceutical companies to invest in developing the new antibiotics we desperately need, and PDUFA reauthorization is an opportunity to do so,” said Jeff Levi, executive director of the Trust for America's Health, an advocacy organization, in the news release. “Rich or poor, all of us are dependent on the development of effective new antibiotics.”

Some of the groups that signed the Feb. 22 letter (PDF) include the IDSA, the American College of Emergency Physicians, the Children's Hospital Association, the National Foundation for Infectious Diseases and Premier.

The organizations wrote that “a combination of push and pull incentives is needed to sufficiently raise the net present value of antibiotics so that they may compete on a level playing field with other drug categories for companies' R&


Read more
: Groups urge incentives for antibiotic research - Healthcare business news and research | Modern

Europe's response to the problem of antibiotic shortage

Europe's response to the problem of antibiotic shortage

Feb 25, 2912

Brussels - The issues of antibiotic shortage and growing resistance of many microorganisms to antibiotics is a significant global health issue. Strategies to tackle this issue have varied worldwide.
European Union wide data published by the European Centre for Disease Prevention and Control (ECDC) on antibiotic resistance has shown that resistance to last-line antibiotics is increasing in Europe (last-line refers to the fact that many bacteria are now resistant to the older generation of antibacterials; last-line refers to the last set of effective antibiotics available). Resistance by pathogens which frequently cause pneumonia and urinary tract infections in hospitals is increasing across the EU and is now established in several countries. These are the 'super bugs' (or multidrug resistant bacteria).
Many bacteria have become resistant to antibiotics through the widespread (some would say overuse) of antibiotics. It is well established that exposing bacteria to the right antibiotics kills most of them. However, the antibiotics course often leaves a few mutants behind that happen to resist the drug better than the rest. These mutants go on to multiply, and, over the course of many years and between many people, eventually the whole strain evolves resistance. Scientists have got round this by developing new generations of antibiotics. The problem now facing the world is that the latest generation may be the last, at least it is becoming increasingly difficult to formulate new antibiotics.
With Europe, the European Centre for Disease Prevention and Control (ECDC) has recently announced a strategy to tackle this issue.
According to the ECDC director, Dr. Marc Sprenger:
"The goal of this Europe-wide health initiative is to support national campaigns on prudent use of antibiotics. Overuse of antibiotics, both in hospitals and in the community, is one of the major drivers of drug resistance in bacteria. ECDC collects EU-wide data on these resistant bacteria, mostly from laboratories testing blood samples taken in hospitals. New data, released by ECDC today, shows that antibiotic resistance is increasing across the EU."
This has lead to a five year plan to address antibiotic issues. The key steps of the plan, displayed on the European Commission website, are:
a) Improve awareness raising on the appropriate use of antimicrobials
b) Strengthen EU law on veterinary medicines and on medicated feed
c) Introduce recommendations for prudent use of antimicrobials in veterinary medicine
d) Strengthen infection prevention and control in hospitals, clinics, etc.
e) Introduce legal tools to tighten prevention and control of infections in animals in the new EU Animal Health Law
f) Promote unprecedented collaboration to bring new antimicrobials to patients
g) Promote efforts to analyse the need for new antibiotics in veterinary medicine
h) Develop and/or strengthen multilateral and bilateral commitments for the prevention and control of AMR
i) Strengthen surveillance systems on AMR and antimicrobial consumption in human medicines
j) Strengthen surveillance systems on AMR and antimicrobial consumption in animal medicines
k) Reinforce and co-ordinate research
l) Improve communication on AMR to the public.
The purpose of the ECDC's focused is summarized in a press release:
"For a large part, antibiotic resistance is being driven by misuse of antibiotics in humans and animals. According to the latest data released by ESAC (European Surveillance of Antimicrobial Consumption), the vast majority of human consumption of antibiotics occurs in the community. Resistance to last-line antibiotics like the carbapenems, however, cannot be explained only by the use of antibiotics outside hospitals. Studies show that 50% of all antibiotic use in hospitals can be inappropriate. Prudent use of antibiotics is paramount to prevent and control resistant bacteria. Additionally, compliance with good hand hygiene by healthcare workers is the most effective way to prevent the spread of infections in hospitals. Finally, there is a particular lack of new antibiotics with new targets of mechanisms of action, in particular against carbapenem-resistant Gram-negative bacteria."

Read more: Digital Journal



Friday, February 24, 2012

Antibiotics Don't Help Most Sinus Infections

Antibiotics Don't Help Most Sinus Infections


by Shamir Benji; February 22, 2012

Sinus infections are not pleasant. They often present with a runny nose, cough, pain around the face, fever and generalized fatigue. While some individuals may never develop a sinus infection, there are other unlucky people who tend to develop recurrent episodes of sinusitis.

Sinusitis often makes it difficult to work, breath and sleep. It can even confine one to the home.

Most individuals quickly go to their physician for treatment of the nasal drip and congested nasal passages. For the most part, doctors readily prescribe a variety of antibiotics for sinus infections.

It is estimated that nearly 20 percent of all antibiotics prescribed today are for sinus or ear infections. (3) This represents millions of doses of antibiotics with a cost running into billions of dollars for the consumer.

Now that may all be changing. A new study questions the wisdom of routinely prescribing antibiotic for sinus infections. The latest study suggests that instead of immediately prescribing antibiotics, the doctors should monitor the patient to determine if they develop worsening of the symptoms.

In this study conducted by Dr Jane Garbutt from Washington University School of Medicine, St. Louis, patients treated with antibiotic for their sinus infections only had a small improvement compared to people who were treated with a placebo (sugar pill).

So what is the explanation for these confounding results?

Dr. Garbutt indicated that in most cases, sinus infections are due to viruses and not bacteria. Since viruses do not respond to antibiotics, there will be no difference in outcome even when one is prescribed these drugs.

It is only the rare patient who may have a bacterial sinus infection but unfortunately the doctor cannot tell by just looking whether it is a viral or bacterial infection. (1)

Based on these observations, doctors are advised to follow the patients and only prescribe antibiotics to patients whose symptoms are getting worse.

In the last three decades there has been great concern that antibiotics are liberally prescribed by physicians. While these medications are useful, prolonged and unnecessary usage has led to development of drug resistance and of course, there is also a potential for side effects.

One of the biggest problems with overuse of antibiotics has been the emergence of methicilin-resistant staphylococcus aureus.

How this study will change doctor's practice in the treatment of sinus infections remains to be seen. Many physicians still continue to prescribe antibiotics for ear infections and bronchitis despite clinical evidence showing that these disorders are due to viruses and not bacteria. (2)

For the consumer, this does not mean that sinusitis does not have to be treated at all. The infection often presents with a variety of annoying symptoms which can easily be treated with home remedies.

The odd ache and facial pain can be treated with over-the-counter pain medications like Motrin. Moreover, these medications will also help reduce the fever.

It is difficult to prevent sinus infections when living in a cool temperate climate but immediately rushing to a physician at the first sign of symptoms is not recommended. Since most sinus infections are viral, try home remedies first.

Only if the symptoms persist for more than seven days, a visit to the doctor may be worthwhile. This will not only save you money but also the agony of waiting for hours before you get seen by the doctor.


Zinc plus antibiotics saves lives of children with pneumonia, study finds

Zinc plus antibiotics saves lives of children with pneumona, study finds


Zinc used in addition to antibiotics significantly reduced mortality in children ages 6 months to 59 months with severe pneumonia when compared with antibiotics alone, according to the findings of a recent study done in Uganda.

The study, published online February 8 in BMC Medicine, also indicated that the adjunct therapy had a greater effect among HIV-infected children than those who were not infected with HIV.

The double-blind, randomized, placebo-controlled study was led by Maheswari G. Srinivasan, from the Department of Pediatrics and Child Health at the School of Medicine, in Uganda. Researchers enrolled 352 children, aged 6 months to 59 months, who were admitted to the Mulago Hospital pediatric emergency ward with severe pneumonia between September 2006 and March 2007.

"There are 2 key findings in this study: overall, zinc supplementation in these children significantly decreased case fatality, but did not reduce the time to normalization of the parameters for disease severity," the authors stated, noting that these findings come from the secondary objective rather than the primary objectives, which were to assess the effect of zinc as an adjunct therapy on time to normalization of respiratory rate, temperature, and oxygen saturation.

The investigators randomly assigned the children to receive standard antibiotic therapy plus zinc (10 mg for children aged under 12 months; 20 mg for children 12 months and older) or standard antibiotic therapy plus placebo daily. The children were assessed every 6 hours for the first 48 hours and then every 12 hours for 7 days of treatment.

The investigators found no evidence that zinc decreased length of time to recovery. They did, however, note the number of deaths was lower among the children who were treated with zinc (4.0% vs 11.9%; RR=0.33; 95% CI, 0.15-0.76).

In addition, the researchers noted that the effect of zinc supplementation appeared stronger among children infected with HIV. There were more deaths among HIV-positive children assigned to placebo compared with those who received zinc (25.9% vs 0%; RR=0.1; 95% CI, 0.0-1.0).

Among those children who were not infected with HIV and who received placebo, the death rate was 5.5% versus 3.9% among HIV-uninfected children who received zinc (RR=0.7; 95% CI, 0.2-2.2).

“Acute respiratory tract infections are the most common cause of morbidity and deaths in children less than 5 years,” the authors wrote in their background. “Given these results,” the authors stated, “zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapy-naïve, HIV-infected children in our environment.”

Potential Antibiotics Alternative to Treat Infection Without Resistance

Potential Antibiotics Alternative to Treat Infection Without Resistance

Curious Cat Science and Engineering Blog | Thursday, February 23, 2012

Researchers at the University of Michigan have found a potential alternative to conventional antibiotics that could fight infection with a reduced risk of antibiotic resistance. Sadly Michigan is another school that is allowing work of those paid for by the citizens of Michigan to be lock away, only due to the wishes of an outdated journal business model instead of supporting open science. The Big Ten seems much more interested in athletic riches than in promoting science. The Big Ten should be ashamed of such anti knowledge behavior and require open science for their schools if they indeed value knowledge.

By using high-throughput screening of a library of small molecules, the team identified a class of compounds that significantly reduced the spread and severity of group A Streptococcus (GAS) bacteria in mice. Their work suggests that the compounds might have therapeutic value in the treatment of strep and similar infections in humans.

“The widespread occurrence of antibiotic resistance among human pathogens is a major public health problem,” said David Ginsburg, a faculty member at LSI, a professor of internal medicine, human genetics, and pediatrics at the U-M Medical School and a Howard Hughes Medical Institute investigator.

Ginsburg led a team that included Scott Larsen, research professor of medicinal chemistry and co-director of the Vahlteich Medicinal Chemistry Core at U-M’s College of Pharmacy, and Hongmin Sun, assistant professor of medicine at the University of Missouri School of Medicine.

Work on this project is continuing at U-M and the University of Missouri, including the preparation of new compounds with improved potency and the filing of patents, Larsen said. Large research schools are also very interested in patents. That is ok, though seems to cloud the pursuit of knowledge too often when too large a focus is on dollars at many schools. But, it seems to put the schools primary focus on dollars; education seems to start to be a minor activity at some of these large schools.

Current antibiotics interfere with critical biological processes in the pathogen to kill it or stop its growth. But at the same time, stronger strains of the harmful bacteria can sometimes resist the treatment and flourish.

An alternate approach is to suppress the virulence of the infection but still allow the bacteria to grow, which means there is no strong selection for strains that are resistant to antibiotics. In a similar experiment at Harvard University, an anti-virulence strategy was successful in protecting mice from cholera.

About 700 million people have symptomatic group A Streptococcus infections around the world each year, and the infection can be fatal. Most doctors prescribe penicillin. The newly identified compounds could work with conventional antibiotics and result in more effective treatment.

How Using Antibiotics in Animal Feed Creates Superbugs

How Using Antibiotics in Animal Feed Creates Superbugs

Many livestock groups say there's no evidence that antibiotics in livestock feed have caused a human health problem, but researchers beg to differ.

Researchers have nailed down something scientists, government officials and agribusiness proponents have argued about for years: whether antibiotics in livestock feed give rise to antibiotic-resistant germs that can threaten humans.

A study in the journal mBio, published by the American Society for Microbiology, shows how an antibiotic-susceptible staph germ passed from humans into pigs, where it became resistant to the antibiotics tetracycline and methicillin. And then the antibiotic-resistant staph learned to jump back into humans.

"It's like watching the birth of a superbug," says Lance Price of the Translational Genomics Research Institute, or TGen, in Flagstaff, Ariz.

Price and colleagues in 19 countries did whole-genome analysis on a staph strain called CC398 and 88 closely related variations. CC398 is a so-called MRSA, or methicillin-resistant Staphylococcus aureus, that emerged within the past decade in pigs and has since spread widely in cattle and poultry as well as pigs.

The genetic analysis allowed the study authors to trace the lineage of the livestock bug back to its antibiotic-susceptible human ancestors. Price says it shows beyond a doubt that the animal bacterium jumped back into humans with close exposure to livestock.

This "pig MRSA" has been detected in nearly half of all meat sampled in U.S. commerce, according to the American Society for Microbiology. Most staph found in meat can be eliminated by cooking food well, but it can still pose a risk to consumers if handled unsafely or if it cross-contaminates with other things in the kitchen.

Price told The Salt that the new resistant human bug appears to be spreading beyond people with direct exposure to livestock.

"Initially we could always trace it back to livestock exposure," Price says. "But now we are starting to see cases of resistant strains that we can't trace back. So we think it may be changing gears, so to speak, and gaining the capacity to be passed from person to person."

Price says the new data provide an early warning of what might become a major public health problem.

"We're seeing this one coming," he says. "The question is how often will this occur in the future if we don't start controlling antibiotic use?"

So far, the proportion of human MRSA infections due to this livestock-derived strain is small. But in some areas of the Netherlands, it's causing as many as 1 in 4 human MRSA cases — suggesting that it has the potential to spread extensively.

Paul Keim, another study author, says the report shows that "our inappropriate use of antibiotics ... is now coming back to haunt us." He says the solution is clear — banning antibiotics in livestock feed, as the European Union has done.

Most antibiotics sold in the U.S. go to animals, mostly in their feed, where they act as a growth promoter and damp down infection outbreaks in large feedlots.

Many livestock groups say there's no evidence that using antibiotics in livestock feed creates a human health problem.

"Most informed scientists and public health professionals acknowledge that the problem of antibiotic resistance in humans is overwhelmingly an issue related to human antibiotic use," the American Meat Institute says.

The new report adds fuel to the long-running debate about antibiotic use for livestock, and the government's responsibility to regulate it. In December, the FDA withdrew a 1977 proposal to remove approvals for two antibiotics, penicillins and tetracyclines, used in livestock and poultry feed. It said it would focus instead on "voluntary reform" by the meat industry to limit use.

Then in a partial reversal in January, the agency said it would ban one class of antibiotics called cephalosporins from animal feed.

Thursday, February 16, 2012

Redesign of Glycopeptide Antibiotics - Back to the Future.

Redesign of Glycopeptide Antibiotics - Back to the Future.


Feb 2012

Abstract


The glycopeptide antibiotics are the most important class of drugs used in the treatment of resistant bacterial infections including those caused by methicillin-resistant Staphylococcus aureus (MRSA). After more than 50 years of clinical use, the emergence of glycopeptide resistant Gram-positive pathogens such as vancomycin-resistant enterococci (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA) presents a serious global challenge to public health at a time few newantibiotics are being developed. This has led to renewed interest in the search for additional effective treatments including the development of new derivatives of the glycopeptide antibiotics. General approaches have been explored for modifying glycopeptide antibiotics, typically through the derivatization of the natural products themselves or more recently through chemical total synthesis. In this Perspective, we consider recent efforts to redesign glycopeptide antibiotics for the treatment of resistant microbial infections, including VRE and VRSA, and examine their potential for providing an even more powerful class of antibiotics that are even less prone to bacterial resistance.


ACS Chemical Biology

Monday, February 13, 2012

Polymyxin use associated with respiratory arrest.

Polymyxin use associated with respiratory arrest.


2012 Feb

Source

Department of Anesthesiology, Columbia University, 622 W 168th St, PH5-527D, New York, NY 10032. hw2125@columbia.edu.

Abstract


The polymyxins (polymyxin B and E) are bactericidal polypeptide antibiotics first discovered in 1947 and used for the treatment of gram-negative bacterial infections. Renal and neurologic toxicities coupled with the increasing availability of effective alternatives led to declining use in the 1960s. The emergence of multidrug-resistant organisms in the past decade has resulted in a resurgence in the use of polymyxins in critically ill patients, yet the side effects are not well known. We report two cases of respiratory arrest likely due to polymyxin B infusions in the context of a 10-fold increase in the use of polymyxin B in our institution over the past 10 years.


Chest ACCP Publications