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

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.

EmpowHer

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

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

Publish date: Feb 24, 2012
By: Formulary staff

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.”

Modern Medicine

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.

ECNMag.com

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.

NPR

Redesign of Glycopeptide Antibiotics - Back to the Future.

Feb 2012

Boger DL, James RC, Pierce JG, Okano A, Xie J.

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

Polymyxin use associated with respiratory arrest.

2012 Feb

Wunsch H, Moitra VK, Patel M, Dzierba AL.

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

Paper supported immunosensor for detection of antibiotics.

2012 Jan

Wu X, Kuang H, Hao C, Xing C, Wang L, Xu C.

Source

School of Food Science & Technology, State Key Lab of Food Science & Technology, Jiangnan University, Wuxi 214122, China.

Abstract

Keywords

• Immunosensor;
• Paper;
• Antibiotics;
• Single-walled carbon nanotube

Paper supports were used to develop a simple, inexpensive, fast and sensitive electrochemical immunosensor for the analysis of antibiotic residues in milk samples, where single-walled carbon nanotubes (SWNTs) and a simple dip-dry coating method were employed to prepare the highly sensitive biosensor. Well-dispersed SWNTs were impregnated with an antibody against neomycin to obtain a composite coating solution, followed by dipping the filtration paper in the solution to fabricate the sensitive biosensor which had high electrical conductivity. Based on the impedance change in the entire paper supported biosensor with increased concentrations of neomycin, the limit detection of the optimized method was 0.04ngmL(-1) and a linear detection range from 0.2 to 125ngmL(-1), well below the European Union regulations for neomycin in this matrix. This paper supported biosensor was applied to determine neomycin in milk samples after a simple sample treatment, with spiked recoveries which ranged from 93.25 to 110.47%. A variety of antibiotic residues in milk samples could be determined following similar sensor preparation.

Elsevier

Antibiotics as immunomodulant agents in COPD.

Feb 2012

Blasi F, Mantero M, Aliberti S.

Source

Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, University of Milan, IRCCS Fondazione Cà Granda Ospedale Maggiore, Milan, Italy.

Abstract

It is widely accepted that some antibiotics have activities beyond their direct antibacterial effects. Macrolide is the antibiotic class with more convincing studies and evidence on its immunomodulatory and anti-inflammatory activities. Different clinical studies have shown that macrolide prophylaxis in patients with moderate-severe chronic obstructive pulmonary disease (COPD) can have a significant impact on the exacerbation rate reducing morbidity and, potentially, mortality of the disease. Other antibiotics, such as fluoroquinolones, demonstrate a variety of immunomodulatory effects but only few clinical data are available in COPD. New macrolide derivatives devoid of antibacterial activity have been synthetized. This review analyses the relevance of immunomodulatory and anti-inflammatory effects of antibiotics in the management of COPD.

PubMed

Factors affecting the prescribing patterns of antibiotics and injections.

Feb 2012

Choi KH, Park SM, Lee JH, Kwon S.

Source

Department of Health Policy and Management, School of Public Health, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Abstract

There are serious problems concerning the inadequate prescription of antibiotics and overuse of injections in primary care. However, the determinants of prescription patterns in Korea are not well-documented. To examine the area characteristics affecting the prescription of antibiotics and injections in primary care practices in the treatment of respiratory tract infections (RTIs), a nationwide cross-sectional study was performed in all 250 administrative districts of Korea.

The outcome was modeled as a binary variable: over-prescription or not compared with the nation-wide average. Over-prescription of antibioticswas associated with the ratio of specialists to general physicians and over-prescription in previous years in the area (adjusted odds ratio [aOR], 4.8; 95% confidence interval [CI] 1.5-14.8; and aOR, 12.0; 95% CI 5.5-25.9, respectively). Over-use of injections was associated with younger population, urban living and the number of hospital beds in the area (aOR, 0.2; 95% CI 0.1-0.4; aOR, 0.3; 95% CI 0.1-0.8; and aOR, 0.4, 95% CI 0.2-0.9; respectively).

There were differences in the prescribing patterns in different districts; prescription patterns were affected more by supply factors than by demand factors. Highly competitive medical environment associated with supply factors is a significant determinant of prescription patterns in Korea.

PubMed

Polymyxin use associated with respiratory arrest.

Feb 2012

Wunsch H, Moitra VK, Patel M, Dzierba AL.

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.

PubMed

Clarithromycin Use and Risk of Death in Patients with Ischemic Heart Disease

Cardiology. 2010 Jun

Andersen SS, Hansen ML, Norgaard ML, Folke F, Fosbøl EL, Abildstrøm SZ, Raunsø J, Madsen M, Køber L, Gislason GH, Torp-Pedersen C.

Department of Cardiology, Gentofte Hospital, Copenhagen, Denmark.

Abstract

Objectives: To examine whether treatment with clarithromycin was associated with an increased risk of death in patients with preexisting ischemic heart disease (IHD).

Methods: Employing nationwide registers, all patients with IHD events from 1997 to 2007 who subsequently claimed prescriptions for dual antibiotic treatment for eradication treatment were identified. The primary endpoint was all-cause mortality.

Results: The study included 214,330 individuals with IHD; 5,265 (2.5 %) of these claimed prescriptions for dual antibiotics. Compared with IHD patients not undergoing eradication therapy, no increase in the risk of all-cause mortality was demonstrated (HR 1.02; 95% CI 0.84-1.23, p = 0.87) after 5 years. Conclusions: The use of clarithromycin in the setting of eradication treatment for Helicobacter pylori in patients with IHD was not associated with an increased risk of death.

Pubmed