Bioaccumulation of Antibiotic Pollution in Marine Food Webs

Antibiotic Pollution in Marine Food Webs in Laizhou Bay, North China: Trophodynamics and Human Exposure Implication

2017 Study Abstract

Little information is available about the bioaccumulation and biomagnification of antibiotics in marine food webs.

Here, we investigate the levels and trophic transfer of 9 sulfonamide (SA), 5 fluoroquinolone (FQ), and 4 macrolide (ML) antibiotics, as well as trimethoprim in nine invertebrate and ten fish species collected from a marine food web in Laizhou Bay, North China in 2014 and 2015.

All the antibiotics were detected in the marine organisms, with SAs and FQs being the most abundant antibiotics. Benthic fish accumulated more SAs than invertebrates and pelagic fish, while invertebrates exhibited higher FQ levels than fish.

Antibiotic Pollution in Marine Food Webs in Laizhou Bay, North China: Trophodynamics and Human Exposure Implication, Environmental Science & Technology, DOI: 10.1021/acs.est.6b04556, January 20, 2017.

Generally, SAs and trimethoprim biomagnified in the food web, while the FQs and MLs were biodiluted. Trophic magnification factors (TMF) were 1.2–3.9 for SAs and trimethoprim, 0.3–1.0 for FQs and MLs. Limited biotransformation and relatively high assimilation efficiencies are the likely reasons for the biomagnification of SAs. The pH dependent distribution coefficients (log D) but not the lipophilicity (log KOW) of SAs and FQs had a significant correlation (r = 0.73; p < 0.05) with their TMFs.

Although the calculated estimated daily intakes (EDI) for antibiotics suggest that consumption of seafood from Laizhou Bay is not associated with significant human health risks, this study provides important insights into the guidance of risk management of antibiotics.

Common veterinary antibiotics not quickly biodegradable infiltrate our aquatic environment

Which factors make drugs persistent? A look at sulphonamides in Polish rivers

Pharmaceutical pollution is a growing environmental concern in the EU, as the world’s second biggest consumer of human medicinal products. Up to 90% of orally administered drugs are excreted in the urine of animals and people1 , which means medicinal products can infiltrate the aquatic environment, where they may have negative effects on wildlife.

This study focused on sulphonamides, a group of chemicals used mainly as anti-bacterial agents. Although sulphonamides are now rarely used in human medicine, they remain important in animal medicine; in agriculture, up to 58 milligrams of sulphonamide can be used to produce just 1 kilogram of meat. As a result, levels of these drugs can reach 400 milligrams per kilogram in manure. The presence of these chemicals in the environment could promote drug resistance in bacteria in soil. After leaching into nearby water bodies, the drugs could also have negative impacts on aquatic organisms.

Which factors make drugs persistent? A look at sulphonamides in Polish rivers, Science for Environment Policy, 12 January 2017.

Assessment of the biodegradability of selected sulfa drugs in two polluted rivers in Poland: Effects of seasonal variations, accidental contamination, turbidity and salinity, science direct, August 2016.

Image credit PracticalCures.

Various factors are key to assessing the risk from a chemical, including its toxicological properties and how quickly it is broken down — the latter being the focus of this study. Chemicals that persist in the environment pose a risk because they can accumulate up the food chain, enabling them to reach potentially toxic levels. Some persistent chemicals can also move long distances, allowing them to travel far from their source.

According to the guidelines of the Stockholm Convention, substances with a half-life in the aquatic environment of over two months (i.e. it takes over two months for the chemical to break down to 50% of its original concentration) can be classified as persistent. Stockholm Convention parties, including the EU, are required to implement special procedures for such substances. Data suggest that the half-life of some sulphonamides is over two months, yet they are not considered persistent organic pollutants.

Many factors can affect the biodegradation rate of sulphonamides, such as the amount of light, the pH of the water and the presence of oxygen. This study investigated the biodegradability of four sulphonamides: sulphanilamide, sulpha-methoxazole, sulphadiazine and sulphathiazole. The researchers investigated the influence of weather conditions, water quality and experimental procedure on the breakdown of these sulphonamides in water samples collected from rivers in Poland.

A total of 19 water samples were collected from two highly polluted Polish rivers. Both rivers flow through one of the EU’s largest urban areas (the Upper Silesian Industrial Region), which has over 12 active coal mines and metallurgical industries and a human population of around 3 million. Immediately after sampling, a concentrated solution of sulphonamides was added to the water. The researchers quantified the concentration of the drugs in each sample over 28 days.

Before commencing biodegradation experiments, the researchers assessed the effect of sulphonamides on microorganisms in the water. After 18 hours of incubation, significant growth inhibition was observed, but after two days this inhibition decreased. This suggests that microorganisms are inhibited by the drugs but, over time, adapt to their presence.

Next, the researchers looked at how each drug was broken down by microbes (biodegraded). Microbial activity and thus biodegradation can depend on the effect of individual chemicals as well as external conditions such as temperature, leading to complex interactions.

Sulpha-methoxazole was the most resistant to biodegradation, with an average half-life of 72 days — meeting the definition of a persistent organic pollutant. As sulpha-methoxazole is the most commonly used sulphonamide in veterinary medicine and the most frequently detected in environmental samples, this result could be of environmental concern. Sulphathiazole was the most biodegradable, and had similar rates of biodegradation to the other two drugs, which were also rapidly broken down.

It is not only the type of sulphonamide that affects biodegradation. The researchers found that the factor with the biggest effect on biodegradation was temperature, with rates of breakdown significantly lower during the colder, winter season.

In Central European areas, vegetation increases with temperature from spring to autumn, leading to more biodiversity, higher microbial activity and a higher rate of biodegradation. However, during wintertime, temperatures drop and vegetation is suppressed, leading to reduced microbial activity and thus reduced biodegradation. This suggests the environmental risk associated with sulphonamides could be higher in the winter.

The authors also found a connection with pH, with acidity reducing degradation, and salt content (salinity), with higher salinity also reducing degradation (suggesting that removing salt from wastewater entering rivers could increase drug breakdown). Lower turbidity (the cloudiness of water, caused by particles it contains) also reduced breakdown, because the particles found in water support microorganisms. Finally, heavy-metal contamination from nearby industrial sites also inhibited sulphonamide degradation.

This study shows that various factors can reduce the biodegradation of sulphonamides and that risk may be particularly acute during winter, although further research is needed to clarify the ecological risk these compounds pose under different conditions

Diethylstilbestrol Exposure and Leukemia, Brain Tumors, Wilms’ tumor

Childhood cancer: overview of incidence trends and environmental carcinogens

Abstract

An estimated 8000 children 0 to 14 years of age are diagnosed annually with cancer in the United States. Leukemia and brain tumors are the most common childhood malignancies, accounting for 30 and 20% of newly diagnosed cases, respectively.

From 1975 to 1978 to 1987 to 1990, cancer among white children increased slightly from 12.8 to 14.1/100,000. Increases are suggested for leukemia, gliomas, and, to a much lesser extent, Wilms’ tumor.

There are a few well-established environmental causes of childhood cancer such as radiation, chemotherapeutic agents, and diethylstilbestrol.

Childhood cancer: overview of incidence trends and environmental carcinogens, Environ Health Perspectives, NCBI PubMed PMID: 8549470, 1995 Sep.

Image of Sam via MLlive.

Many other agents such as electromagnetic fields, pesticides, and some parental occupational exposures are suspected of playing roles, but the evidence is not conclusive at this time.

Some childhood exposures such as secondhand cigarette smoke may contribute to cancers that develop many years after childhood.

For some exposures such as radiation and pesticides data suggest that children may be more susceptible to the carcinogenic effects than similarly exposed adults.

Diethylstilbestrol exposure and Medications

Transplacental carcinogenesis was established by the discovery in 1971 of vaginal adenocarcinoma in the daughters of women who took the hormone diethylstilbestrol (DES) during pregnancy to avoid miscarriages. This very rare cancer has been detected in girls as young as 7 years old, with most affected between 15 and 22 years of age. There are concerns that at older ages the exposed daughters may also have increased risk of squamous carcinomas of the vagina and cervix and cancers of the breast and that exposed sons may have excess testicular and prostate cancer . Continued followup of the DES-exposed daughters and sons is ongoing at the National Cancer Institute and may provide further information on the late effects of DES and on transplacental carcinogenesis in general.

Suspected, but less well-established, of being a transplacental carcinogen is phenytoin, an antiepileptic drug. There are reports of neuroblastoma and soft tissue sarcoma in children exposed in utero to phenytoin.

There have also been reports of excess brain tumors, neuroblastomas, leukemia, and retinoblastomas in children of women who used antinausea medications (e.g., Bendectin) during pregnancy. This issue had received considerable publicity, however, which may have affected recall of use by study subjects. One study used medical records, not subject recall, to assess exposure and did not show any associations.

There is one report of excess Wilms’ tumor among Swedish children whose mothers were exposed to penthrane (methoxyflurane) anesthesia during delivery. The excess risk was higher in females and increased with age at diagnosis.

Some medical treatments received during childhood also play a role in the development of childhood cancer. Chemotherapy and radiation therapy received for an initial childhood cancer can dramatically increase the risk for second cancers. For example, in one study children treated with alkylating agents for cancer have a 5-fold risk of subsequently developing leukemia. At high doses, the risk was increased as much as 25 times the expected rate of leukemia. Bone sarcomas were also elevated in children treated with radiation and chemotherapy.

The potent antibiotic chloramphenicol, given to treat life-threatening infectious conditions, has been linked to excess acute lymphocytic leukemia and acute nonlymphocytic leukemia in children in Shanghai. This association with leukemia is consistent with a report of bone marrow depression following use of chloramphenicol.

Parental use of illegal drugs has been linked to childhood cancer in a few reports. Marijuana use was associated with rhabdomyosarcoma, leukemia, and brain tumors. Cocaine use was also associated with rhabdomyosarcoma.

These exposures are difficult to study accurately and need further research, but prevention efforts clearly must continue for noncancer-related reasons even in the absence of convincing data on childhood cancer.

Click to dowload the complete article.

More DES DiEthylStilbestrol Resources

Inpatient Antibiotic Use Among US Hospitals

Antibiotics Are Still Overused in Hospitals

The most comprehensive study yet shows that antibiotic use hasn’t changed in hospitals, despite recent warnings that they drugs are overprescribed.

ABSTRACT

Objective
To use proprietary administrative data to estimate patterns of US inpatient antibiotic use in recent years.

Design, Setting, and Participants
For this retrospective analysis, adult and pediatric in-patient antibiotic use data was obtained from the Truven Health MarketScan Hospital Drug Database (HDD) from January 1, 2006, to December 31, 2012. Data from adult and pediatric patients admitted to 1 of approximately 300 participating acute care hospitals provided antibiotic use data for over 34 million discharges representing 166 million patient-days.

Estimating National Trends in Inpatient Antibiotic Use Among US Hospitals From 2006 to 2012, jama network, September 19, 2016.

Main Outcomes and Measures
We retrospectively estimated the days of therapy (DOT) per 1000 patient-days and the proportion of hospital discharges in which a patient received at least 1 dose of an antibiotic during the hospital stay. We calculated measures of antibiotic usage stratified by antibiotic class, year, and other patient and facility characteristics. We used data submitted to the Centers for Medicare and Medicaid Services Healthcare Cost Report Information System to generate estimated weights to apply to the HDD data to create national estimates of antibiotic usage. A multivariate general estimating equation model to account for interhospital covariance was used to assess potential trends in antibiotic DOT over time.

Results
During the years 2006 to 2012, 300 to 383 hospitals per year contributed antibiotic data to the HDD. Across all years, 55.1% of patients received at least 1 dose of antibiotics during their hospital visit. The overall national DOT was 755 per 1000 patient-days. Overall antibiotic use did not change significantly over time. The multivariable trend analysis of data from participating hospitals did not show a statistically significant change in overall use (total DOT increase, 5.6; 95% CI, −18.9 to 30.1; P = .65). However, the mean change (95% CI) for the following antibiotic classes increased significantly: third- and fourth-generation cephalosporins, 10.3 (3.1-17.5); macrolides, 4.8 (2.0-7.6); glycopeptides, 22.4 (17.5-27.3); β-lactam/β-lactamase inhibitor combinations, 18.0 (13.3-22.6); carbapenems, 7.4 (4.6-10.2); and tetracyclines, 3.3 (2.0-4.7).

Conclusions and Relevance
Overall DOT of all antibiotics among hospitalized patients in US hospitals has not changed significantly in recent years. Use of some antibiotics, especially broad spectrum agents, however, has increased significantly. This trend is worrisome in light of the rising challenge of antibiotic resistance. Our findings can help inform national efforts to improve antibiotic use by suggesting key targets for improvement interventions.

How do You like your Shrimps? With Antibiotics, Chlorine, or Diesel?

Shrimp: buyer beware, by Martha Rosenberg

Martha Rosenberg, writing for the Organic Consumers Association, tells us what shrimp production is like today. When it comes to eating shrimp, it’s buyer beware…

” … In Bangladesh, … the “chemical soup” that commercial shrimp are grown in threatens local workers, and pollutes their water bodies and marine life with toxic effluent. When the ponds become so polluted that even antibiotics no longer work, the operators pack up and move on to a new location… ”

” Commercial shrimp production in India, the second largest exporter of shrimp to the U.S, begins with a long list of chemicals, including urea, superphosphate and diesel. … Fish-killing chemicals like chlorine and rotenone (linked to Parkinson’s Disease), and the use of Borax and sodium tripolyphosphate (a suspected neurotoxin), are rampant in India’s shrimp production. ”

” … formalin is approved for use in U.S. shrimp production. Formalin is a parasiticide which contains formaldehyde gas. It has no mandatory withdrawal time or legal residue tolerance. Other chemicals … are “unapproved” but widely used “off-label”. “

Read Contemporary Shrimp Production Poses Risks to Consumers and the Environment, organicconsumers, by Martha Rosenberg, August 10, 2016.

Wastewater treatment plant discharges can promote the development of antibiotic resistance genes in streams

Occurrence and persistence of antibiotic resistance genes in river biofilms after wastewater inputs in small rivers

Widespread use of antibiotics has led to pollution of waterways, potentially creating resistance among freshwater bacterial communities. A new study looked for antibiotic resistance genes in a river basin in Spain, revealing that wastewater discharges can promote the spread of antibiotic resistance in streams and small rivers.

Abstract

Occurrence and persistence of antibiotic resistance genes in river biofilms after wastewater inputs in small rivers, ScienceDirect, Environmental Pollution, Volume 210, March 2016, Pages 121–128.

The extensive use of antibiotics in human and veterinary medicine and their subsequent release into the environment may have direct consequences for autochthonous bacterial communities, especially in freshwater ecosystems. In small streams and rivers, local inputs of wastewater treatment plants (WWTPs) may become important sources of organic matter, nutrients and emerging pollutants, such as antibiotic resistance genes (ARGs).

In this study, we evaluated the effect of WWTP effluents as a source of ARGs in river biofilms. The prevalence of genes conferring resistance to main antibiotic families, such as beta-lactams (blaCTX-M), fluoroquinolones (qnrS), sulfonamides (sul I), and macrolides (ermB), was determined using quantitative PCR (qPCR) in biofilm samples collected upstream and downstream WWTPs discharge points in four low-order streams. Our results showed that the WWTP effluents strongly modified the hydrology, physico-chemistry and biological characteristics of the receiving streams and favoured the persistence and spread of antibiotic resistance in microbial benthic communities. It was also shown that the magnitude of effects depended on the relative contribution of each WWTP to the receiving system. Specifically, low concentrations of ARGs were detected at sites located upstream of the WWTPs, while a significant increase of their concentrations was observed in biofilms collected downstream of the WWTP discharge points (particularly ermB and sul I genes). These findings suggest that WWTP discharges may favour the increase and spread of antibiotic resistance among streambed biofilms. The present study also showed that the presence of ARGs in biofilms was noticeable far downstream of the WWTP discharge (up to 1 km).

It is therefore reasonable to assume that biofilms may represent an ideal setting for the acquisition and spread of antibiotic resistance determinants and thus be considered suitable biological indicators of anthropogenic pollution by active pharmaceutical compounds.

Tell KFC to stop supersizing antibiotic resistance

Treating livestock with antibiotics is leading to a rise in drug-resistant superbugs

Kentucky Fried Chicken is pumping antibiotics into the meats used to make its famous chickens. The World Health Organization has warned that this practice could push us into a ‘post antibiotic era,’ in which the drugs we rely on for routine medical treatments no longer work. Investors have spoken out about these concerns. But KFC isn’t listening.

Will you tell Roger Eaton, Yum Brands & KFC CEO, to stop the excessive use of antibiotics? Use this link to sign the petition.

Press Releases

  • Tell KFC to stop serving chicken raised with antibiotics!, change.
  • Consumer groups press Yum’s KFC to tighten antibiotic rules, reuters, Aug 10, 2016.
  • KFC told to stop using chicken treated with antibiotics, BBC News Business, 10 August 2016.
  • 350,000 sign petition against KFC’s use of antibiotics as superbug fears mount, Independent, 11 August 2016.

You might wish to watch those videos about antibiotics overuse in farming.

Tell McDonald’s to stop supersizing antibiotic resistance

Treating livestock with antibiotics is leading to a rise in drug-resistant superbugs

McDonald’s is pumping antibiotics into the meats used to make its famous burgers. The World Health Organization has warned that this practice could push us into a ‘post antibiotic era,’ in which the drugs we rely on for routine medical treatments no longer work. Investors have spoken out about these concerns. But McDonald’s isn’t listening.

Will you tell Steve Easterbrook, McDonald’s CEO, to stop the excessive use of antibiotics? Use this link to email him.

Press Releases

  • Public join investors in telling McDonald’s: don’t supersize antibiotics, shareaction, August 12, 2016.
  • McDonald’s pressured to serve up global antibiotics ban, BBC News Business, 12 August 2016.

You might wish to watch those videos about antibiotics overuse in farming.

Saving antibiotics for when they are really needed: the Dutch example

The Netherlands demonstrated that antibiotic use can be reduced in agriculture

Dutch healthcare uses the fewest antibiotics in the world,” is the bold and justifiable claim of the Dutch Health Council, the government’s independent scientific advisers. The country has had low use for decades. Yet in veterinary medicine the Netherlands, the world’s second largest exporter of agri-food products (after the United States), was, until a few years ago, among the highest users. This mismatch sparked action that saw the country cut antibiotic use in farm animals by nearly 60% from 2007 to 2015.

Today the Netherlands has one of the lowest levels of antimicrobial resistance in the world, and it believes the only way to keep resistance levels down is for health and agricultural sectors everywhere to work together in what it calls a “One Health” approach.

“If we want to control a problem in healthcare we need to act everywhere where antibiotics are used. Because of the continuous evolution of resistance, any reservoir could be a source of resistant organisms to humans,”

says Dik Mevius, head of the National Reference Laboratory on Antimicrobial Resistance in Animals at the Central Veterinary Institute at Wageningen University.

The Dutch have shown that antibiotic use can be slashed in agriculture too.
So why isn’t everybody doing it?

Read Saving antibiotics for when they are really needed: the Dutch example, The BMJ 2016;354:i4192, 03 August 2016.

Drug-resistant bacteria found in streams and small rivers near wastewater discharges

Wastewater treatment plant discharges can promote the development of antibiotic resistance in streams

Antibiotics are a cornerstone of modern medicine and have saved millions of lives. However, their extensive use has led to the development of widespread resistance, rendering them ineffective against some infections. Microorganisms resistant to commonly prescribed antibiotics are increasingly being found, leading the World Health Organization to declare antibiotic resistance a ‘major threat to public health’. Already, approximately 25 000 European citizens die every year from infections caused by bacteria resistant to antibiotics.

Wastewater treatment plant discharges can promote the development of antibiotic resistance in streams, Science for Environment Policy News Alert, 08 April 2016.

Although some bacteria are intrinsically resistant to antibiotics, and resistant strains evolve naturally, the overuse of antibiotics accelerates this process. Drug-resistant bacteria can pass on resistance to other bacteria, via a process called ‘horizontal gene transfer’, which is thought to be the major cause of the spread of resistance among bacteria.

While the clinical side of this problem has been studied extensively, there is a less-studied environmental aspect. Antibiotics are not fully metabolised by animals (including humans), which means that residues can enter the aquatic environment via wastewater discharges. Recent studies have shown that concentrations of antibiotics found in aquatic environments could aid selection of resistant bacteria. Inputs from urban wastewater treatment plants (WWTPs) can also include antibiotic-resistant bacteria and resistance genes.

Occurrence and persistence of antibiotic resistance genes in river biofilms after wastewater inputs in small rivers, ScienceDirect, Environmental Pollution, Volume 210, March 2016, Pages 121–128.

This study is one of very few to assess antibiotic resistance in river biofilms: the layer of slime composed of microbial organisms that is found on rocks, plants and other surfaces in rivers. Antibiotic-resistant bacteria can integrate into these biofilms, which may provide an optimal environment for the exchange of genetic material, including genes encoding resistance to antibiotics.

The researchers, who were part-funded by the European Regional Development Fund, evaluated the abundance of antibiotic resistance genes in the Tordera River Basin in northern Spain, which receives input from domestic WWTPs. They looked for genes conferring resistance to major families of antibiotics in biofilm samples collected upstream and downstream of WWTP discharge points in four streams.

The monitored genes confer resistance to antibiotics commonly used in hospitals and communities (such as fluoroquinolones, macrolides and sulfonamides). Previous studies have shown a high prevalence of these genes in water samples collected from Mediterranean rivers.

WWTPs are necessary to minimise, inter alia, organic pollution from wastewater generated by human settlements, which would otherwise affect water bodies and the wider environment. Despite the overall positive role of WWTPs, the results of the study showed that WWTP discharges can strongly affect the hydrology and physical, chemical and biological characteristics of receiving streams.

In the study, WWTPs increased stream flow, water conductivity and nitrogen/phosphorus content. They also significantly increased the abundance of antibiotic resistance genes downstream. For example, the ermB gene (which confers resistance to erythromycin, an antibiotic used to treat respiratory infections) occurred four times more frequently in biofilms collected downstream of WWTPs than in those collected upstream. The extent of the changes was influenced by the relative contribution of each WWTP. The authors say their findings suggest WWTP discharges support the spread of antibiotic resistance in streams.

The researchers found antibiotic resistance genes as far as 1 km downstream of the WWTPs, which suggests resistance genes can persist in the environment even in the absence of an additional pollution source, perhaps due to the ‘drift’ of antibiotic-resistant bacteria or resistance genes in the water flow. Alternatively, resistant bacteria or resistance genes could have entered the river from unknown sources located between the WWTP discharge site and the site 1 km downstream.

The authors say further studies are needed to determine the reason for the increase in antibiotic resistance in biofilms downstream of the WWTPs. It could have resulted from the release of resistant bacteria from the WWTPs, or from indigenous bacteria becoming resistant in response to the presence of antibiotic residues discharged into the streams. Overall, the researchers say river biofilms could be useful as indicators of anthropogenic pollution with pharmaceutical residues.

If wastewater discharges negatively affect the quality of a water body, for example by increasing the level of an antibiotic above an established environmental quality standard (EQS), measures must be taken by Member States to improve the water quality. At present, EQS for pollutants are set in relation to their toxic (or similar) effects on organisms. For antibiotics, account may also need to be taken of their role in triggering the development of resistance in bacteria, and of the significance of that resistance.