Knowledge of antibiotics and antibiotic resistance in patients followed by family physicians.

PubMed

Robert, A; Nguyen, Y; Bajolet, O; Vuillemin, B; Defoin, B; Vernet-Garnier, V; Drame, M; Bani-Sadr, F

2017-03-01

We aimed to evaluate factors associated with knowledge of antibiotics and drug resistance. A questionnaire was handed out by 14 family physicians to their patients between December 20, 2014 and April 20, 2015 in Rethel (North-East of France). We conducted a cross-sectional study using a logistical regression model to assess factors associated with antibiotic knowledge. Three criteria were used to assess that knowledge. Overall, 293 questionnaires were analysed; 48% of patients had received antibiotics in the previous 12 months. Only 44% and 26% gave a correct answer for the statements "Antibiotics are effective against bacteria and ineffective against viruses" and "Antibiotic resistance decreases if the antibiotic use decreases", respectively. Characteristics such as female sex, age>30 years, high level of education, high professional categories, and having received antibiotic information by the media were associated with high level of knowledge about antibiotics and/or antibiotic resistance. In contrast, having received antibiotic information from family physicians was not associated with good knowledge. Although media awareness campaigns had an independent impact on a higher public knowledge of antibiotics, the overall public knowledge remains low. It would be necessary to strengthen antibiotic campaigns with clearer information on the relation between the excessive use of antibiotics and the increased risk of antibiotic resistance. Family physicians should be more involved to improve antibiotic knowledge among target groups such as men, young patients, and people from a poor social and cultural background. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Antibiotic Resistance in Sepsis Patients: Evaluation and Recommendation of Antibiotic Use

PubMed Central

Pradipta, Ivan Surya; Sodik, Dian Chairunnisa; Lestari, Keri; Parwati, Ida; Halimah, Eli; Diantini, Ajeng; Abdulah, Rizky

2013-01-01

Background: The appropriate selection of empirical antibiotics based on the pattern of local antibiotic resistance can reduce the mortality rate and increase the rational use of antibiotics. Aims: We analyze the pattern of antibiotic use and the sensitivity patterns of antibiotics to support the rational use of antibiotics in patients with sepsis. Materials and Methods: A retrospective observational study was conducted in adult sepsis patient at one of Indonesian hospital during January-December 2011. Data were collected from the hospital medical record department. Descriptive analysis was used in the processing and interpretation of data. Results: A total of 76 patients were included as research subjects. Lung infection was the highest source of infection. In the 66.3% of clinical specimens that were culture positive for microbes, Klebsiella pneumoniae, Escherichia coli, Staphylococcus hominis were detected with the highest frequency. The six most frequently used antibiotics, levofloxacin, ceftazidime, ciprofloxacin, cefotaxime, ceftriaxone, and erythromycin, showed an average resistance above 50%. Conclusions: The high use of antibiotic with a high level resistance requires a policy to support its rational use. Local microbial pattern based on site infection and pattern of antibiotics sensitivity test can be used as supporting data to optimize appropriateness of empirical antibiotics therapy in sepsis patients. PMID:23923107

DEVELOPMENT OF AN ANTIBIOTIC OPTIONS INDEX FOR ANTIBIOTIC RESISTANCE MONITORING.

PubMed

Manomayitthikan, Taweesuk; Borlace, Glenn N; Kessomboon, Nusaraporn

2016-11-01

Using antibiogram data to indicate the overall antibiotic resistance of a pathogen is complicated by the multiple antibiotic susceptibilities reported in the antibiogram. The objectives of this study were to develop and determine the benefits of an Antibiotic Options Index (AOI); an index that summarizes antibiotic susceptibility data for a pathogen by presenting it as the availability of antibiotic treatment options. The AOI was calculated using antibiogram data for the seven most commonly isolated pathogens from the National Antimicrobial Resistance Surveillance Center of Thailand between 1998 and 2014 and was classified as acceptable (AOI ≥ 0.8) or unacceptable (AOI < 0.8) based on the availability of treatment options. The AOI identified two problematic pathogens: Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA). For A. baumannii, the probability of having at least two viable antibiotic treatment options (AOIm2) decreased from an acceptable level (0.93) in 1998 to an unacceptable level (0.53) in 2014 and for MRSA the AOIm2 decreased from an acceptable level (0.82) in 1998 to an unacceptable level (0.47) in 2014. By including the idea that the problem with increasing antibiotic resistance is a problem with treating infections, the AOI effectively compiles susceptibility data to present it as the probability of having effective antibiotic treatment. This index is calculated from widely available antibiogram data, making it more suitable to be used to monitor antibiotic resistance at the hospital, provincial and national levels.

Containing antibiotic resistance: decreased antibiotic-resistant coliform urinary tract infections with reduction in antibiotic prescribing by general practices

PubMed Central

Butler, Chris C; Dunstan, Frank; Heginbothom, Margaret; Mason, Brendan; Roberts, Zoë; Hillier, Sharon; Howe, Robin; Palmer, Stephen; Howard, Anthony

2007-01-01

Background GPs are urged to prescribe antibiotics less frequently, despite lack of evidence linking reduced antibiotic prescribing with reductions in resistance at a local level. Aim To investigate associations between changes in antibiotic dispensing and changes in antibiotic resistance at general-practice level. Design of study Seven-year study of dispensed antibiotics and antibiotic resistance in coliform isolates from urine samples routinely submitted from general practice. Setting General practices in Wales. Method Multilevel modelling of trends in resistance to ampicillin and trimethoprim, and changes in practice total antibiotic dispensing and amoxicillin and trimethoprim dispensing. Results The primary analysis included data on 164 225 coliform isolates from urine samples submitted from 240 general practices over the 7-year study period. These practices served a population of 1.7 million patients. The quartile of practices that had the greatest decrease in total antibiotic dispensing demonstrated a 5.2% reduction in ampicillin resistance over the 7-year period with changes of 0.4%, 2.4%, and −0.3% in the other three quartiles. There was a statistically significant overall decrease in ampicillin resistance of 1.03% (95% confidence interval [CI] = 0.37 to 1.67%) per decrease of 50 amoxicillin items dispensed per 1000 patients per annum. There were also significant reductions in trimethoprim resistance in the two quartiles of practices that reduced total antibiotic dispensing most compared with those that reduced it least, with an overall decrease in trimethoprim resistance of 1.08% (95% CI = 0.065 to 2.10%) per decrease of 20 trimethoprim items dispensed per 1000 patients per annum. Main findings were confirmed by secondary analyses of 256 370 isolates from 527 practices that contributed data at some point during the study period. Conclusion Reducing antibiotic dispensing at general-practice level is associated with reduced local antibiotic resistance

Background antibiotic resistance patterns in antibiotic-free pastured poultry production

USDA-ARS?s Scientific Manuscript database

Antibiotic resistance (AR) is a significant public health issue, and agroecosystems are often viewed as major environmental sources of antibiotic resistant foodborne pathogens. While the use of antibiotics in agroecosystems can potentially increase AR, appropriate background resistance levels in th...

Antibiotics and antibiotic resistance: a bitter fight against evolution.

PubMed

Rodríguez-Rojas, Alexandro; Rodríguez-Beltrán, Jerónimo; Couce, Alejandro; Blázquez, Jesús

2013-08-01

One of the most terrible consequences of Darwinian evolution is arguably the emergence and spread of antibiotic resistance, which is becoming a serious menace to modern societies. While spontaneous mutation, recombination and horizontal gene transfer are recognized as the main causes of this notorious phenomenon; recent research has raised awareness that sub-lethal concentrations of antibiotics can also foster resistance as an undesirable side-effect. They can produce genetic changes by different ways, including a raise of free radicals within the cell, induction of error-prone DNA-polymerases mediated by SOS response, imbalanced nucleotide metabolism or affect directly DNA. In addition to certain environmental conditions, subinhibitory concentrations of antimicrobials may increase, even more, the mutagenic effect of antibiotics. Here, we review the state of knowledge on antibiotics as promoters of antibiotic resistance. Copyright © 2013 Elsevier GmbH. All rights reserved.

Newly approved antibiotics and antibiotics reserved for resistant infections: Implications for emergency medicine.

PubMed

Mazer-Amirshahi, Maryann; Pourmand, Ali; May, Larissa

2017-01-01

Millions of patients are evaluated every year in the emergency department (ED) for bacterial infections. Emergency physicians often diagnose and prescribe initial antibiotic therapy for a variety of bacterial infections, ranging from simple urinary tract infections to severe sepsis. In life-threatening infections, inappropriate choice of initial antibiotic has been shown to increase morbidity and mortality. As such, initiation of appropriate antibiotic therapy on the part of the emergency physician is critical. Increasing rates of antibiotic resistance, drug allergies, and antibiotic shortages further complicates the choice of antibiotics. Patients may have a history of prior resistant infections or culture data indicating that common first-line antibiotics used in the ED may be ineffective. In recent years, there have been several new antibiotic approvals as well as renewed interest in second and third line antibiotics because of the aforementioned concerns. In addition, several newly approved antibiotics have the advantage of being administered once weekly or even as a single infusion, which has the potential to decrease hospitalizations and healthcare costs. This article reviews newly approved antibiotics and antibiotics used to treat resistant infections with a focus on implications for emergency medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Outpatient Antibiotic Use and the Need for Increased Antibiotic Stewardship Efforts.

PubMed

Zetts, Rachel M; Stoesz, Andrea; Smith, Brian A; Hyun, David Y

2018-06-01

Antibiotic-resistant infections pose a growing threat to public health. Antibiotic use, regardless of whether it is warranted, is a primary factor in the development of resistance. In the United States, the majority of antibiotic health care expenditures are due to prescribing in outpatient settings. Much of this prescribing is inappropriate, with research showing that at least 30% of antibiotic use in outpatient settings is unnecessary. In this State of the Art Review article, we provide an overview of the latest research on outpatient antibiotic prescribing practices in the United States. Although many of the researchers in these studies describe antibiotic prescribing across all patient age groups, we highlight prescribing in pediatric populations when data are available. We then describe the various factors that can influence a physician's prescribing decisions and drive inappropriate antibiotic use and the potential role of behavioral science in enhancing stewardship interventions to address these drivers. Finally, we highlight the role that a wide range of health care stakeholders can play in aiding the expansion of outpatient stewardship efforts that are needed to fully address the threat of antibiotic resistance. Copyright © 2018 by the American Academy of Pediatrics.

Antibiotic adjuvants - A strategy to unlock bacterial resistance to antibiotics.

PubMed

González-Bello, Concepción

2017-09-15

Resistance to available antibiotics in pathogenic bacteria is currently a global challenge since the number of strains that are resistant to multiple types of antibiotics has increased dramatically each year and has spread worldwide. To unlock this problem, the use of an 'antibiotic adjuvant' in combination with an antibiotic is now being exploited. This approach enables us to prolong the lifespan of these life-saving drugs. This digests review provides an overview of the main types of antibiotic adjuvants, the basis of their operation and the remaining issues to be tackled in this field. Particular emphasis is placed on those compounds that are already in clinical development, namely β-lactamase inhibitors. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

RecA Inhibitors Potentiate Antibiotic Activity and Block Evolution of Antibiotic Resistance.

PubMed

Alam, Md Kausar; Alhhazmi, Areej; DeCoteau, John F; Luo, Yu; Geyer, C Ronald

2016-03-17

Antibiotic resistance arises from the maintenance of resistance mutations or genes acquired from the acquisition of adaptive de novo mutations or the transfer of resistance genes. Antibiotic resistance is acquired in response to antibiotic therapy by activating SOS-mediated DNA repair and mutagenesis and horizontal gene transfer pathways. Initiation of the SOS pathway promotes activation of RecA, inactivation of LexA repressor, and induction of SOS genes. Here, we have identified and characterized phthalocyanine tetrasulfonic acid RecA inhibitors that block antibiotic-induced activation of the SOS response. These inhibitors potentiate the activity of bactericidal antibiotics, including members of the quinolone, β-lactam, and aminoglycoside families in both Gram-negative and Gram-positive bacteria. They reduce the ability of bacteria to acquire antibiotic resistance mutations and to transfer mobile genetic elements conferring resistance. This study highlights the advantage of including RecA inhibitors in bactericidal antibiotic therapies and provides a new strategy for prolonging antibiotic shelf life. Copyright © 2016 Elsevier Ltd. All rights reserved.

Access to antibiotics in New Delhi, India: implications for antibiotic policy.

PubMed

Kotwani, Anita; Holloway, Kathleen

2013-01-01

The present survey was conducted to investigate the price and availability of a basket of 24 essential antibiotics and eight high-end antibiotics at various levels of health care in public and private sector in National Capital Territory of Delhi, India using standardized WHO/HAI methodology. DATA ON PROCUREMENT PRICE AND AVAILABILITY WAS COLLECTED FROM THREE PUBLIC HEALTHCARE PROVIDERS IN THE STATE: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Overall a total of 83 public facilities, 68 primary care, 10 secondary cares and 5 tertiary care facilities were surveyed. Data was also collected from private retail (n = 40) and chain pharmacies (n = 40) of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR). PUBLIC SECTOR: Delhi state government has its essential medicine list (Delhi state EML) and was using Delhi state EML 2007 for procurement; the other two agencies had their own procurement list. All the antibiotics procured including second and third generation antibiotics except for injections were available at primary care facilities. Antibiotic available were on the basis of supply rather than rationality or the Delhi state EML and none was 100% available. There was sub-optimal availability of some essential antibiotics while other non-essential ones were freely available. Availability of antibiotics at tertiary care facilities was also sub-optimal. Private sector: Availability of antibiotics was good. For most of the antibiotics the most expensive and popular trade names were often available. High-end antibiotics, meropenam, gemifloxacin, and moxifloxacin were commonly available. In retail pharmacies some newer generation non-essential antibiotics like gemifloxacin were priced lower than the highest-priced generic of amoxicillin + clavulanic acid, azithromycin, and cefuroxime aexitl. Inappropriate availability and pricing of newer

Access to antibiotics in New Delhi, India: implications for antibiotic policy

PubMed Central

2013-01-01

Objective The present survey was conducted to investigate the price and availability of a basket of 24 essential antibiotics and eight high-end antibiotics at various levels of health care in public and private sector in National Capital Territory of Delhi, India using standardized WHO/HAI methodology. Methods Data on procurement price and availability was collected from three public healthcare providers in the state: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Overall a total of 83 public facilities, 68 primary care, 10 secondary cares and 5 tertiary care facilities were surveyed. Data was also collected from private retail (n = 40) and chain pharmacies (n = 40) of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR). Results Public sector: Delhi state government has its essential medicine list (Delhi state EML) and was using Delhi state EML 2007 for procurement; the other two agencies had their own procurement list. All the antibiotics procured including second and third generation antibiotics except for injections were available at primary care facilities. Antibiotic available were on the basis of supply rather than rationality or the Delhi state EML and none was 100% available. There was sub-optimal availability of some essential antibiotics while other non-essential ones were freely available. Availability of antibiotics at tertiary care facilities was also sub-optimal. Private sector: Availability of antibiotics was good. For most of the antibiotics the most expensive and popular trade names were often available. High-end antibiotics, meropenam, gemifloxacin, and moxifloxacin were commonly available. In retail pharmacies some newer generation non-essential antibiotics like gemifloxacin were priced lower than the highest-priced generic of amoxicillin + clavulanic acid, azithromycin, and cefuroxime aexitl. Conclusions Inappropriate

Antibiotic Capture by Bacterial Lipocalins Uncovers an Extracellular Mechanism of Intrinsic Antibiotic Resistance

PubMed Central

El-Halfawy, Omar M.; Klett, Javier; Ingram, Rebecca J.; Loutet, Slade A.; Murphy, Michael E. P.; Martín-Santamaría, Sonsoles

2017-01-01

ABSTRACT The potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. Here we show that a soluble bacterial lipocalin produced by Burkholderia cenocepacia upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics in vitro and in vivo. These phenotypes were recapitulated by heterologous expression in B. cenocepacia of lipocalin genes from Pseudomonas aeruginosa, Mycobacterium tuberculosis, and methicillin-resistant Staphylococcus aureus. Purified lipocalin bound different classes of bactericidal antibiotics and contributed to bacterial survival in vivo. Experimental and X-ray crystal structure-guided computational studies revealed that lipocalins counteract antibiotic action by capturing antibiotics in the extracellular space. We also demonstrated that fat-soluble vitamins prevent antibiotic capture by binding bacterial lipocalin with higher affinity than antibiotics. Therefore, bacterial lipocalins contribute to antimicrobial resistance by capturing diverse antibiotics in the extracellular space at the site of infection, which can be counteracted by known vitamins. PMID:28292982

Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants.

PubMed

Pontes, Daniela Santos; de Araujo, Rodrigo Santos Aquino; Dantas, Natalina; Scotti, Luciana; Scotti, Marcus Tullius; de Moura, Ricardo Olimpio; Mendonca-Junior, Francisco Jaime Bezerra

2018-01-01

The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs are important to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Non-antibiotic antimicrobial triclosan induces multiple antibiotic resistance through genetic mutation.

PubMed

Lu, Ji; Jin, Min; Nguyen, Son Hoang; Mao, Likai; Li, Jie; Coin, Lachlan J M; Yuan, Zhiguo; Guo, Jianhua

2018-06-11

Antibiotic resistance poses a major threat to public health. Overuse and misuse of antibiotics are generally recognized as the key factors contributing to antibiotic resistance. However, whether non-antibiotic, anti-microbial (NAAM) chemicals can directly induce antibiotic resistance is unclear. We aim to investigate whether the exposure to a NAAM chemical triclosan (TCS) has an impact on inducing antibiotic resistance on Escherichia coli. Here, we report that at a concentration of 0.2 mg/L TCS induces multi-drug resistance in wild-type Escherichia coli after 30-day TCS exposure. The oxidative stress induced by TCS caused genetic mutations in genes such as fabI, frdD, marR, acrR and soxR, and subsequent up-regulation of the transcription of genes encoding beta-lactamases and multi-drug efflux pumps, together with down-regulation of genes related to membrane permeability. The findings advance our understanding of the potential role of NAAM chemicals in the dissemination of antibiotic resistance in microbes, and highlight the need for controlling biocide applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antibiotics involved in the occurrence of antibiotic-resistant bacteria: a nationwide multilevel study suggests differences within antibiotic classes.

PubMed

Gbaguidi-Haore, Houssein; Dumartin, Catherine; L'Hériteau, François; Péfau, Muriel; Hocquet, Didier; Rogues, Anne-Marie; Bertrand, Xavier

2013-02-01

To identify the antibiotics potentially the most involved in the occurrence of antibiotic-resistant bacteria from an ecological perspective in French healthcare facilities (HCFs). This study was based on data from the French antimicrobial surveillance network (ATB-RAISIN, 2007-09). Antibiotics were expressed in defined daily doses per 1000 patient-days. Antibiotic-resistant bacteria were considered as count data adjusted for patient-days. These were third-generation cephalosporin (3GC)- and ciprofloxacin-resistant Escherichia coli, cefotaxime-resistant Enterobacter cloacae, methicillin-resistant Staphylococcus aureus and ceftazidime-, imipenem- and ciprofloxacin-resistant Pseudomonas aeruginosa. Three-level negative binomial regression models were built to take into account the hierarchical structure of data: level 1, repeated measures each year (count outcome, time, antibiotics); level 2, HCFs (type and size); and level 3, regions (geographical area). A total of 701 HCFs from 20 French regions and up to 1339 HCF-years were analysed. The use of ceftriaxone, but not of cefotaxime, was positively correlated with incidence rates of 3GC- and ciprofloxacin-resistant E. coli. In contrast, both 3GCs were positively correlated with the incidence rate of cefotaxime-resistant E. cloacae. Higher levels of use of ciprofloxacin and/or ofloxacin, but not of levofloxacin, were associated with higher incidence rates of 3GC- and ciprofloxacin-resistant E. coli, cefotaxime-resistant E. cloacae, methicillin-resistant S. aureus and ceftazidime- and ciprofloxacin-resistant P. aeruginosa. Our study suggests differences within antibiotic classes in promoting antibiotic resistance. We identified ceftriaxone, ciprofloxacin and ofloxacin as priority targets in public health strategies designed to reduce antibiotic use and antibiotic-resistant bacteria in French HCFs.

Antibiotics and Breastfeeding.

PubMed

de Sá Del Fiol, Fernando; Barberato-Filho, Silvio; de Cássia Bergamaschi, Cristiane; Lopes, Luciane Cruz; Gauthier, Timothy P

2016-01-01

During the breastfeeding period, bacterial infections can occur in the nursing mother, requiring the use of antibiotics. A lack of accurate information may lead health care professionals and mothers to suspend breastfeeding, which may be unnecessary. This article provides information on the main antibiotics that are appropriate for clinical use and the interference of these antibiotics with the infant to support medical decisions regarding the discontinuation of breastfeeding. We aim to provide information on the pharmacokinetic factors that interfere with the passage of antibiotics into breast milk and the toxicological implications of absorption by the infant. Publications related to the 20 most frequently employed antibiotics and their transfer into breast milk were evaluated. The results demonstrate that most antibiotics in clinical use are considered suitable during breastfeeding; however, the pharmacokinetic profile of each drug must be observed to ensure the resolution of the maternal infection and the safety of the infant. © 2016 S. Karger AG, Basel.

Antibiotic Safety

MedlinePlus

... specific to women Antibiotics can lead to vaginal yeast infections. This happens because antibiotics kill the normal bacteria in the vagina and this causes yeast to grow rapidly. Symptoms of a yeast infection ...

Incentives for new antibiotics: the Options Market for Antibiotics (OMA) model.

PubMed

Brogan, David M; Mossialos, Elias

2013-11-07

Antimicrobial resistance is a growing threat resulting from the convergence of biological, economic and political pressures. Investment in research and development of new antimicrobials has suffered secondary to these pressures, leading to an emerging crisis in antibiotic resistance. Current policies to stimulate antibiotic development have proven inadequate to overcome market failures. Therefore innovative ideas utilizing market forces are necessary to stimulate new investment efforts. Employing the benefits of both the previously described Advanced Market Commitment and a refined Call Options for Vaccines model, we describe herein a novel incentive mechanism, the Options Market for Antibiotics. This model applies the benefits of a financial call option to the investment in and purchase of new antibiotics. The goal of this new model is to provide an effective mechanism for early investment and risk sharing while maintaining a credible purchase commitment and incentives for companies to ultimately bring new antibiotics to market. We believe that the Options Market for Antibiotics (OMA) may help to overcome some of the traditional market failures associated with the development of new antibiotics. Additional work must be done to develop a more robust mathematical model to pave the way for practical implementation.

Antibiotic-non-antibiotic combinations for combating extremely drug-resistant Gram-negative 'superbugs'.

PubMed

Schneider, Elena K; Reyes-Ortega, Felisa; Velkov, Tony; Li, Jian

2017-02-28

The emergence of antimicrobial resistance of Gram-negative pathogens has become a worldwide crisis. The status quo for combating resistance is to employ synergistic combinations of antibiotics. Faced with this fast-approaching post-antibiotic era, it is critical that we devise strategies to prolong and maximize the clinical efficacy of existing antibiotics. Unfortunately, reports of extremely drug-resistant (XDR) Gram-negative pathogens have become more common. Combining antibiotics such as polymyxin B or the broad-spectrum tetracycline and minocycline with various FDA-approved non-antibiotic drugs have emerged as a novel combination strategy against otherwise untreatable XDR pathogens. This review surveys the available literature on the potential benefits of employing antibiotic-non-antibiotic drug combination therapy. The apex of this review highlights the clinical utility of this novel therapeutic strategy for combating infections caused by 'superbugs'. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Novel antibiotics: are we still in the pre-post-antibiotic era?

PubMed

Draenert, R; Seybold, U; Grützner, E; Bogner, J R

2015-04-01

Therapeutic efficacy and safety in infections due to multidrug-resistant bacteria can be improved by the clinical development of new compounds and devising new derivatives of already useful antibiotics. Due to a striking global increase in multidrug-resistant Gram-positive but even more Gram-negative organisms, new antibiotics are urgently needed. This paper provides a review of novel antibiotic compounds which are already in clinical development, mainly in phase III clinical trials. Each of these new trials increases the possibility of new antibiotics receiving approval.

Comparative outcomes of β-lactam antibiotics in outpatient parenteral antibiotic therapy: treatment success, readmissions and antibiotic switches.

PubMed

Lee, Boeun; Tam, Idy; Weigel, Bernard; Breeze, Janis L; Paulus, Jessica K; Nelson, Jason; Allison, Genève M

2015-08-01

β-Lactam antibiotics are commonly used in outpatient parenteral antimicrobial therapy (OPAT), but data regarding outcomes of long-term therapy are limited. The purpose of this study was to compare treatment success, readmission and antibiotic switch rates in patients treated with β-lactam antibiotics as OPAT. We carried out a retrospective review of all patients, discharged from Tufts Medical Center with cefazolin, ceftriaxone, ertapenem or oxacillin, between January 2009 and June 2013. A competing risks analysis was used to compare the cumulative incidence of first occurrence of treatment success, antibiotic switch and 30 day readmission for each drug. Four hundred patients were identified (cefazolin n = 38, ceftriaxone n = 104, ertapenem n = 128 and oxacillin n = 130). Baseline demographics were similar. Treatment success rates were higher for ceftriaxone and ertapenem (cefazolin 61%, ceftriaxone 81%, ertapenem 73% and oxacillin 58%; P < 0.001). Thirty-day all-cause readmissions were similar (cefazolin 21%, ceftriaxone 14%, ertapenem 20% and oxacillin 15%; P = 0.46). In 400 OPAT courses, 37 out of 50 antibiotic switches were accomplished without readmission. Adverse drug events (ADEs) were the most common reason for outpatient antibiotic switches (31/37, 84%). The ADE rate was higher for the oxacillin group (cefazolin 2.0 versus ceftriaxone 1.5 versus ertapenem 2.9 versus oxacillin 8.4 per 1000 OPAT days; P < 0.001). OPAT with β-lactam antibiotics is effective, but antibiotic switches for adverse events were more frequent with oxacillin use. Clinicians should be cognizant of the risk of readmissions and ADEs in OPAT patients, as the value of OPAT lies in reducing patient morbidity and readmissions by managing ADEs and preventing clinical failures. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Antibiotics and antibiotic-resistant bacteria in waters associated with a hospital in Ujjain, India

PubMed Central

2010-01-01

Background Concerns have been raised about the public health implications of the presence of antibiotic residues in the aquatic environment and their effect on the development of bacterial resistance. While there is information on antibiotic residue levels in hospital effluent from some other countries, information on antibiotic residue levels in effluent from Indian hospitals is not available. Also, concurrent studies on antibiotic prescription quantity in a hospital and antibiotic residue levels and resistant bacteria in the effluent of the same hospital are few. Therefore, we quantified antibiotic residues in waters associated with a hospital in India and assessed their association, if any, with quantities of antibiotic prescribed in the hospital and the susceptibility of Escherichia coli found in the hospital effluent. Methods This cross-sectional study was conducted in a teaching hospital outside the city of Ujjain in India. Seven antibiotics - amoxicillin, ceftriaxone, amikacin, ofloxacin, ciprofloxacin, norfloxacin and levofloxacin - were selected. Prescribed quantities were obtained from hospital records. The samples of the hospital associated water were analysed for the above mentioned antibiotics using well developed and validated liquid chromatography/tandem mass spectrometry technique after selectively isolating the analytes from the matrix using solid phase extraction. Escherichia coli isolates from these waters were tested for antibiotic susceptibility, by standard Kirby Bauer disc diffusion method using Clinical and Laboratory Standard Institute breakpoints. Results Ciprofloxacin was the highest prescribed antibiotic in the hospital and its residue levels in the hospital wastewater were also the highest. In samples of the municipal water supply and the groundwater, no antibiotics were detected. There was a positive correlation between the quantity of antibiotics prescribed in the hospital and antibiotic residue levels in the hospital wastewater

[Micromonospora resistence to definite antibiotics and their ability to produce structurally analogous antibiotics].

PubMed

Bibikova, M V; Ivanitskaia, L P; Tikhonova, A S

1980-01-01

Thirty six cultures of Micromonospora freshly isolated from soil samples were studied with respect to their sensitivity to a number of antibiotics of various structures and modes of action. It was found that all of them were highly sensitive to penicillin, ristomycin, tetracycline, rifampicin, streptomycin, olivomycin, carminomycin and dactinomycin. Significant differences in sensitivity of the Micromonospora cultures were revealed only with respect to gentamicin, tobramicin, erythromycin and lincomycin. Seven cultures were resistant to gentamicin and tobramicin and sensitive to all of the other antibiotics. Broad spectrum antibiotics were isolated from these cultures. The study of the antibiotic chemistry showed that they were 2-desoxystreptamine-containing aminoglycosides. Two cultures proved to be resistant to erythromycin and lincomycin. When identified with the use of antibiotic resistant staphylococcal strains, the crude antibiotic substances isolated from these cultures appeared to be not active against staphylococci resistant to erythromycin and lincomycin. By their chromatograpi- behaviour the antibiotics were close to macrolides. Therefore, it was found that production of aminoglycoside and macrolide antibiotics was most characteristic of Micromonospora. A certain correlation between resistance of Micromonospora to these 2 antibiotic groups and capacity for their production was shown.

Strategies to Minimize Antibiotic Resistance

PubMed Central

Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee

2013-01-01

Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics. PMID:24036486

Incentives for new antibiotics: the Options Market for Antibiotics (OMA) model

PubMed Central

2013-01-01

Background Antimicrobial resistance is a growing threat resulting from the convergence of biological, economic and political pressures. Investment in research and development of new antimicrobials has suffered secondary to these pressures, leading to an emerging crisis in antibiotic resistance. Methods Current policies to stimulate antibiotic development have proven inadequate to overcome market failures. Therefore innovative ideas utilizing market forces are necessary to stimulate new investment efforts. Employing the benefits of both the previously described Advanced Market Commitment and a refined Call Options for Vaccines model, we describe herein a novel incentive mechanism, the Options Market for Antibiotics. Results This model applies the benefits of a financial call option to the investment in and purchase of new antibiotics. The goal of this new model is to provide an effective mechanism for early investment and risk sharing while maintaining a credible purchase commitment and incentives for companies to ultimately bring new antibiotics to market. Conclusions We believe that the Options Market for Antibiotics (OMA) may help to overcome some of the traditional market failures associated with the development of new antibiotics. Additional work must be done to develop a more robust mathematical model to pave the way for practical implementation. PMID:24199835

Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

PubMed

Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

2011-11-01

The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.

Systemic antibiotics in periodontics.

PubMed

Slots, Jørgen

2004-11-01

This position paper addresses the role of systemic antibiotics in the treatment of periodontal disease. Topical antibiotic therapy is not discussed here. The paper was prepared by the Research, Science and Therapy Committee of the American Academy of Periodontology. The document consists of three sections: 1) concept of antibiotic periodontal therapy; 2) efficacy of antibiotic periodontal therapy; and 3) practical aspects of antibiotic periodontal therapy. The conclusions drawn in this paper represent the position of the American Academy of Periodontology and are intended for the information of the dental profession.

Antibiotic Application and Emergence of Multiple Antibiotic Resistance (MAR) in Global Catfish Aquaculture.

PubMed

Chuah, Li-Oon; Effarizah, M E; Goni, Abatcha Mustapha; Rusul, Gulam

2016-06-01

Catfish is one of the most cultivated species worldwide. Antibiotics are usually used in catfish farming as therapeutic and prophylactic agents. In the USA, only oxytetracycline, a combination of sulfadimethoxine and ormetoprim, and florfenicol are approved by the Food Drug Administration for specific fish species (e.g., catfish and salmonids) and their specific diseases. Misuse of antibiotics as prophylactic agents in disease prevention, however, is common and contributes in the development of antibiotic resistance. Various studies had reported on antibiotic residues and/or resistance in farmed species, feral fish, water column, sediments, and, in a lesser content, among farm workers. Ninety percent of the world aquaculture production is carried out in developing countries, which lack regulations and enforcement on the use of antibiotics. Hence, efforts are needed to promote the development and enforcement of such a regulatory structure. Alternatives to antibiotics such as antibacterial vaccines, bacteriophages and their lysins, and probiotics have been applied to curtail the increasing emergence of antibiotic-resistant bacteria due to the imprudent application of antibiotics in aquaculture.

Optimizing Antibiotic Use in Nursing Homes Through Antibiotic Stewardship.

PubMed

Sloane, Philip D; Huslage, Kirk; Kistler, Christine E; Zimmerman, Sheryl

2016-01-01

Antibiotic stewardship is becoming a requirement for nursing homes. Programs should be interdisciplinary and multifaceted; should have support from nursing home administrators; and should aim to promote antibiotics only when needed, not just in case. Recommended components include use of evidence-based guidelines; ongoing monitoring of antibiotic prescriptions, cultures, and study results; monitoring of health outcomes; use of nursing home-specific antibiograms; regular reporting and feedback to medical providers and nurses; and education of residents and families. ©2016 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.

[Antibiotics: present and future].

PubMed

Bérdy, János

2013-04-14

The author discuss the up to date interpretation of the concept of antibiotics and antibiotic research, as well as the present role of various natural, semisynthetic and synthetic antibiotic compounds in various areas of the human therapy. The origin and the total number of all antibiotics and applied antibiotics in the practice, as well as the bioactive microbial metabolites (antibiotics) in other therapeutical, non-antibiotic fields (including agriculture) are also reviewed. The author discusses main problems, such as increasing (poly)resistance, virulence of pathogens and the non-scientific factors (such as a decline of research efforts and their sociological, economic, financial and regulatory reasons). A short summary of the history of Hungarian antibiotic research is also provided. The author briefly discusses the prospects in the future and the general advantages of the natural products over synthetic compounds. It is concluded that new approaches for the investigation of the unlimited possibilities of the living world are necessary. The discovery of new types or simply neglected (micro)organisms and their biosynthetic capabilities, the introduction of new biotechnological and genetic methods (genomics, metagenom, genome mining) are absolutely required in the future.

The hidden societal cost of antibiotic resistance per antibiotic prescribed in the United States: an exploratory analysis.

PubMed

Michaelidis, Constantinos I; Fine, Michael J; Lin, Chyongchiou Jeng; Linder, Jeffrey A; Nowalk, Mary Patricia; Shields, Ryan K; Zimmerman, Richard K; Smith, Kenneth J

2016-11-08

Ambulatory antibiotic prescribing contributes to the development of antibiotic resistance and increases societal costs. Here, we estimate the hidden societal cost of antibiotic resistance per antibiotic prescribed in the United States. In an exploratory analysis, we used published data to develop point and range estimates for the hidden societal cost of antibiotic resistance (SCAR) attributable to each ambulatory antibiotic prescription in the United States. We developed four estimation methods that focused on the antibiotic-resistance attributable costs of hospitalization, second-line inpatient antibiotic use, second-line outpatient antibiotic use, and antibiotic stewardship, then summed the estimates across all methods. The total SCAR attributable to each ambulatory antibiotic prescription was estimated to be $13 (range: $3-$95). The greatest contributor to the total SCAR was the cost of hospitalization ($9; 69 % of the total SCAR). The costs of second-line inpatient antibiotic use ($1; 8 % of the total SCAR), second-line outpatient antibiotic use ($2; 15 % of the total SCAR) and antibiotic stewardship ($1; 8 %). This apperars to be an error.; of the total SCAR) were modest contributors to the total SCAR. Assuming an average antibiotic cost of $20, the total SCAR attributable to each ambulatory antibiotic prescription would increase antibiotic costs by 65 % (range: 15-475 %) if incorporated into antibiotic costs paid by patients or payers. Each ambulatory antibiotic prescription is associated with a hidden SCAR that substantially increases the cost of an antibiotic prescription in the United States. This finding raises concerns regarding the magnitude of misalignment between individual and societal antibiotic costs.

WAAR (World Alliance against Antibiotic Resistance): Safeguarding antibiotics.

PubMed

Carlet, Jean; Rambaud, Claude; Pulcini, Céline

2012-07-09

Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the five next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practicionners, and veterinarians.

Impact of pharmacist intervention on antibiotic use and prophylactic antibiotic use in urology clean operations.

PubMed

Zhou, Y; Ma, L-Y; Zhao, X; Tian, S-H; Sun, L-Y; Cui, Y-M

2015-08-01

The use of prophylactic antibiotics in clean operations was routine in China before 2011. Along with the appeal for using antibiotics rationally by WHO in 2011, China launched a national special rectification scheme on clinical use of antibiotics from April that year. The scheme, aimed at achieving rational use of antibiotics, made pharmacists part of the responsible medical team. Our objective was to describe the impacts of pharmacist intervention on the use of antibiotics, particularly in urology clean operations. Pharmacists participated in antibiotic stewardship programmes of the hospital and urological clinical work and conducted real-time interventions at the same time from 2011 to 2013. Data on the use of antibiotics between 2010 and 2013 in urology were collected. Comparison of the 2013 data with those of 2010 showed that antibiotic use density [AUD= DDDs*100/(The number of patients who were treated the same period*Average days in hospital). DDDs = Total drug consumption (g)/DDD. DDD is the Defined Daily Dose] decreased by 57·8(58·8%); average antibiotic cost decreased by 246·94 dollars; the cost of antibiotics as a percentage of total drug cost decreased by 27·7%; the rate of use of antibiotics decreased from 100% to 7·3%. The study illustrates how an antibiotic stewardship programme with pharmacist participation including real-time interventions can promote improved antibiotic-prescribing and significantly decrease costs. © 2015 John Wiley & Sons Ltd.

The future of antibiotics

PubMed Central

2014-01-01

Antibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on ‘push’ incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed. PMID:25043962

Solving the Antibiotic Crisis.

PubMed

Wright, Gerard D

2015-02-13

Antibiotics are essential for both treating and preventing infectious diseases. Paradoxically, despite their importance as pillars of modern medicine, we are in danger of losing antibiotics because of the evolution and dissemination of resistance mechanisms throughout all pathogenic microbes. This fact, coupled with an inability to bring new drugs to market at a pace that matches resistance, has resulted in a crisis of global proportion. Solving this crisis requires the actions of many stakeholders, but chemists, chemical biologists, and microbiologists must drive the scientific innovation that is required to maintain our antibiotic arsenal. This innovation requires (1) a deep understanding of the evolution and reservoirs of resistance; (2) full knowledge of the molecular mechanisms of antibiotic action and resistance; (3) the discovery of chemical and genetic probes of antibiotic action and resistance; (4) the integration of systems biology into antibiotic discovery; and (5) the discovery of new antimicrobial chemical matter. Addressing these pressing scientific gaps will ensure that we can meet the antibiotic crisis with creativity and purpose.

Research progress on distribution, migration, transformation of antibiotics and antibiotic resistance genes (ARGs) in aquatic environment.

PubMed

Shao, Sicheng; Hu, Yongyou; Cheng, Jianhua; Chen, Yuancai

2018-05-28

Antimicrobial and antibiotics resistance caused by misuse or overuse of antibiotics exposure is a growing and significant threat to global public health. The spread and horizontal transfer of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) by the selective pressure of antibiotics in an aquatic environment is a major public health issue. To develop a better understanding of potential ecological risks die to antibiotics and ARGs, this study mainly summarizes research progress about: (i) the occurrence, concentration, fate, and potential ecological effects of antibiotics and ARGs in various aquatic environments, (ii) the threat, spread, and horizontal gene transfer (HGT) of ARGs, and (iii) the relationship between antibiotics, ARGs, and ARB. Finally, this review also proposes future research direction on antibiotics and ARGs.

Adverse consequences of neonatal antibiotic exposure.

PubMed

Cotten, Charles M

2016-04-01

Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and variation in antibiotic utilization, discusses the emergence of resistant organisms, and presents data from human neonates and animal models demonstrating the impact of antibiotics on the microbiome, and how microbiome alterations impact health. The importance of antibiotic stewardship is also discussed. Infections increase neonatal morbidity and mortality. Furthermore, the clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic-induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs. The review encourages practitioners to assess local antibiotic use with regard to local microbiology, and to adopt steps to reduce infections and use antibiotics wisely.

Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

PubMed Central

Uppu, Divakara S. S. M.; Konai, Mohini M.; Sarkar, Paramita; Samaddar, Sandip; Fensterseifer, Isabel C. M.; Farias-Junior, Celio; Krishnamoorthy, Paramanandam; Shome, Bibek R.; Franco, Octávio L.

2017-01-01

Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells). The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC) clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS) of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms) and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections. PMID:28837596

Inducing optimal substitution between antibiotics under open access to the resource of antibiotic susceptibility.

PubMed

Herrmann, Markus; Nkuiya, Bruno

2017-06-01

This paper designs a bio-economic model to examine the use of substitute antibiotic drugs (analogs) sold by an industry that has open access to the resource of the antibiotic class's susceptibility (treatment effectiveness). Antibiotics are characterized by different expected recovery rates and production costs, which in conjunction with the class's treatment susceptibility determines their relative effectiveness. Our analysis reveals that the high-quality antibiotic drug loses its comparative advantage over time making the low-quality drug the treatment of last resort in the market equilibrium and the social optimum when antibiotic susceptibility cannot replenish. However, when antibiotic susceptibility is renewable, both antibiotics may be used in the long run, and the comparative advantage of the high-quality drug may be restored in the social optimum that allows lowering infection in the long run. We develop the optimal tax/subsidy scheme that would induce antibiotic producers under open access to behave optimally and account for the social cost of infection and value of antibiotic susceptibility. We show that the welfare loss associated with the uncorrected open-access allocation is highest; when the resource of antibiotic susceptibility is non-renewable, high morbidity costs are incurred by individuals, and low social discount rates apply. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Glycopeptide antibiotic biosynthesis.

PubMed

Yim, Grace; Thaker, Maulik N; Koteva, Kalinka; Wright, Gerard

2014-01-01

Glycopeptides such as vancomycin, teicoplanin and telavancin are essential for treating infections caused by Gram-positive bacteria. Unfortunately, the dwindled pipeline of new antibiotics into the market and the emergence of glycopeptide-resistant enterococci and other resistant bacteria are increasingly making effective antibiotic treatment difficult. We have now learned a great deal about how bacteria produce antibiotics. This information can be exploited to develop the next generation of antimicrobials. The biosynthesis of glycopeptides via nonribosomal peptide assembly and unusual amino acid synthesis, crosslinking and tailoring enzymes gives rise to intricate chemical structures that target the bacterial cell wall. This review seeks to describe recent advances in our understanding of both biosynthesis and resistance of these important antibiotics.

History of Antibiotics Research.

PubMed

Mohr, Kathrin I

2016-01-01

For thousands of years people were delivered helplessly to various kinds of infections, which often reached epidemic proportions and have cost the lives of millions of people. This is precisely the age since mankind has been thinking of infectious diseases and the question of their causes. However, due to a lack of knowledge, the search for strategies to fight, heal, and prevent the spread of communicable diseases was unsuccessful for a long time. It was not until the discovery of the healing effects of (antibiotic producing) molds, the first microscopic observations of microorganisms in the seventeenth century, the refutation of the abiogenesis theory, and the dissolution of the question "What is the nature of infectious diseases?" that the first milestones within the history of antibiotics research were set. Then new discoveries accelerated rapidly: Bacteria could be isolated and cultured and were identified as possible agents of diseases as well as producers of bioactive metabolites. At the same time the first synthetic antibiotics were developed and shortly thereafter, thousands of synthetic substances as well as millions of soil borne bacteria and fungi were screened for bioactivity within numerous microbial laboratories of pharmaceutical companies. New antibiotic classes with different targets were discovered as on assembly line production. With the beginning of the twentieth century, many of the diseases which reached epidemic proportions at the time-e.g., cholera, syphilis, plague, tuberculosis, or typhoid fever, just to name a few, could be combatted with new discovered antibiotics. It should be considered that hundred years ago the market launch of new antibiotics was significantly faster and less complicated than today (where it takes 10-12 years in average between the discovery of a new antibiotic until the launch). After the first euphoria it was quickly realized that bacteria are able to develop, acquire, and spread numerous resistance mechanisms

On the local applications of antibiotics and antibiotic-based agents in endodontics and dental traumatology.

PubMed

Mohammadi, Z; Abbott, P V

2009-07-01

Antibiotics are a valuable adjunctive to the armamentarium available to health professionals for the management of bacterial infections. During endodontic treatment and when managing trauma to the teeth, antibiotics may be applied systemically (orally and/or parenterally) or locally (i.e. intra-dentally via irrigants and medicaments). Due to the potential risk of adverse effects following systemic application, and the ineffectiveness of systemic antibiotics in necrotic pulpless teeth and the periradicular tissues, the local application of antibiotics may be a more effective mode for delivery in endodontics. The aim of this article was to review the history, rationale and applications of antibiotic-containing irrigants and medicaments in endodontics and dental traumatology. The search was performed from 1981 to 2008 and was limited to English-language papers. The keywords searched on Medline were 'Antibiotics AND endodontics', 'Antibiotics AND root canal irrigation', 'Antibiotics AND intra-canal medicament', 'Antibiotics AND Dental trauma' and 'Antibiotics AND root resorption'. The reference section of each article was manually searched to find other suitable sources of information. It seems that local routes of antibiotic administration are a more effective mode than systemic applications. Various antibiotics have been tested in numerous studies and each has some advantages. Tetracyclines are a group of bacteriostatic antibiotics with antibacterial substantivity for up to 12 weeks. They are typically used in conjunction with corticosteroids and these combinations have anti-inflammatory, anti-bacterial and anti-resorptive properties, all of which help to reduce the periapical inflammatory reaction including clastic-cell mediated resorption. Tetracyclines have also been used as part of irrigating solutions but the substantivity is only for 4 weeks. Clindamycin and a combination of three antibiotics (metronidazole, ciprofloxacin and minocycline) have also been

Finding alternatives to antibiotics

USDA-ARS?s Scientific Manuscript database

The spread of antibiotic-resistant pathogens requires new treatments. The availability of new antibiotics has severely declined, and so alternatives to antibiotics need to be considered in both animal agriculture and human medicine. Products for disease prevention are different than products for d...

Antibiotic susceptibility of probiotic strains: Is it reasonable to combine probiotics with antibiotics?

PubMed

Neut, C; Mahieux, S; Dubreuil, L J

2017-11-01

The main goal of this study was to determine the in vitro susceptibility of strains collected from marketed probiotics to antibiotics used to treat community-acquired infections. The minimum inhibitory concentrations (MICs) of 16 antibiotics were determined using a gradient strip (E test) or the agar dilution method for fidaxomicin. The probiotics demonstrated various antibiotic patterns. Bacterial probiotics are generally susceptible to most prescribed antibiotics orally administered, whereas yeast probiotics, such as Saccharomyces boulardii, are resistant. Special attention must be paid to co-prescriptions of antibiotics and probiotics to ensure that the probiotic strain is not susceptible. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Antibiotic Allergy in Pediatrics.

PubMed

Norton, Allison Eaddy; Konvinse, Katherine; Phillips, Elizabeth J; Broyles, Ana Dioun

2018-05-01

The overlabeling of pediatric antibiotic allergy represents a huge burden in society. Given that up to 10% of the US population is labeled as penicillin allergic, it can be estimated that at least 5 million children in this country are labeled with penicillin allergy. We now understand that most of the cutaneous symptoms that are interpreted as drug allergy are likely viral induced or due to a drug-virus interaction, and they usually do not represent a long-lasting, drug-specific, adaptive immune response to the antibiotic that a child received. Because most antibiotic allergy labels acquired in childhood are carried into adulthood, the overlabeling of antibiotic allergy is a liability that leads to unnecessary long-term health care risks, costs, and antibiotic resistance. Fortunately, awareness of this growing burden is increasing and leading to more emphasis on antibiotic allergy delabeling strategies in the adult population. There is growing literature that is used to support the safe and efficacious use of tools such as skin testing and drug challenge to evaluate and manage children with antibiotic allergy labels. In addition, there is an increasing understanding of antibiotic reactivity within classes and side-chain reactions. In summary, a better overall understanding of the current tools available for the diagnosis and management of adverse drug reactions is likely to change how pediatric primary care providers evaluate and treat patients with such diagnoses and prevent the unnecessary avoidance of antibiotics, particularly penicillins. Copyright © 2018 by the American Academy of Pediatrics.

Antibiotic resistance in hospitals: a ward-specific random effect model in a low antibiotic consumption environment.

PubMed

Aldrin, Magne; Raastad, Ragnhild; Tvete, Ingunn Fride; Berild, Dag; Frigessi, Arnoldo; Leegaard, Truls; Monnet, Dominique L; Walberg, Mette; Müller, Fredrik

2013-04-15

Association between previous antibiotic use and emergence of antibiotic resistance has been reported for several microorganisms. The relationship has been extensively studied, and although the causes of antibiotic resistance are multi-factorial, clear evidence of antibiotic use as a major risk factor exists. Most studies are carried out in countries with high consumption of antibiotics and corresponding high levels of antibiotic resistance, and currently, little is known whether and at what level the associations are detectable in a low antibiotic consumption environment. We conduct an ecological, retrospective study aimed at determining the impact of antibiotic consumption on antibiotic-resistant Pseudomonas aeruginosa in three hospitals in Norway, a country with low levels of antibiotic use. We construct a sophisticated statistical model to capture such low signals. To reduce noise, we conduct our study at hospital ward level. We propose a random effect Poisson or binomial regression model, with a reparametrisation that allows us to reduce the number of parameters. Inference is likelihood based. Through scenario simulation, we study the potential effects of reduced or increased antibiotic use. Results clearly indicate that the effects of consumption on resistance are present under conditions with relatively low use of antibiotic agents. This strengthens the recommendation on prudent use of antibiotics, even when consumption is relatively low. Copyright © 2012 John Wiley & Sons, Ltd.

Antibiotics, pediatric dysbiosis, and disease.

PubMed

Vangay, Pajau; Ward, Tonya; Gerber, Jeffrey S; Knights, Dan

2015-05-13

Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease phenotypes in adulthood. Antibiotic use during infancy induces imbalances in gut microbiota, called dysbiosis. The gut microbiome's responses to antibiotics and its potential link to disease development are especially complex to study in the changing infant gut. Here, we synthesize current knowledge linking antibiotics, dysbiosis, and disease and propose a framework for studying antibiotic-related dysbiosis in children. We recommend future studies into the microbiome-mediated effects of antibiotics focused on four types of dysbiosis: loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and blooms of pathogens. Establishment of a large and diverse baseline cohort to define healthy infant microbiome development is essential to advancing diagnosis, interpretation, and eventual treatment of pediatric dysbiosis. This approach will also help provide evidence-based recommendations for antibiotic usage in infancy. Copyright © 2015 Elsevier Inc. All rights reserved.

Bacterial cheating limits antibiotic resistance

NASA Astrophysics Data System (ADS)

Xiao Chao, Hui; Yurtsev, Eugene; Datta, Manoshi; Artemova, Tanya; Gore, Jeff

2012-02-01

The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain---which does not contribute to breaking down the antibiotic---may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.

Antibiotics, Pediatric Dysbiosis, and Disease

PubMed Central

Vangay, Pajau; Ward, Tonya; Gerber, Jeffrey S.; Knights, Dan

2017-01-01

Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease phenotypes in adulthood. Antibiotic use during infancy induces imbalances in gut microbiota, called dysbiosis. The gut microbiome’s responses to antibiotics and its potential link to disease development are especially complex to study in the changing infant gut. Here, we synthesize current knowledge linking antibiotics, dysbiosis, and disease and propose a framework for studying antibiotic-related dysbiosis in children. We recommend future studies into the microbiome-mediated effects of antibiotics focused on four types of dysbiosis: loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and blooms of pathogens. Establishment of a large and diverse baseline cohort to define healthy infant microbiome development is essential to advancing diagnosis, interpretation, and eventual treatment of pediatric dysbiosis. This approach will also help provide evidence-based recommendations for antibiotic usage in infancy. PMID:25974298

Prophylactic Antibiotic Use in COPD and the Potential Anti-Inflammatory Activities of Antibiotics.

PubMed

Huckle, Anthony W; Fairclough, Lucy C; Todd, Ian

2018-05-01

Antibiotics have previously demonstrated anti-inflammatory properties, and they have been linked to therapeutic benefit in several pulmonary conditions that feature inflammation. Previous research suggests that these anti-inflammatory properties may be beneficial in the treatment of COPD. This review assesses the potential benefit of prophylactic, long-term, and low-dose antibiotic therapy in COPD, and whether any effects seen are anti-inflammatory in nature. Randomized, controlled trials comparing antibiotic therapy with placebo in subjects with stable COPD were evaluated. Twelve trials involving 3,784 participants and a range of antibiotics were included: azithromycin (6 studies, 1,972 participants), clarithromycin (1 study, 67 participants), erythromycin (3 studies, 254 participants), roxithromycin (1 study, 191 participants), and moxifloxacin (2 studies, 1,198 participants). In vitro, in vivo, and ex vivo experimental study designs exploring the mechanisms via which antibiotics may act in subjects with stable COPD were evaluated. Azithromycin and erythromycin showed the greatest effect in subjects with COPD, with evidence suggesting improvement in exacerbation-related outcomes and health status, as measured by the St George Respiratory Questionnaire. An increase in antibiotic resistance was reported in 2 studies. The macrolide class of antibiotics exhibited convincing anti-inflammatory properties with relevance to COPD, implicating several pathways as potential mechanisms of action. In conclusion, the therapeutic benefit of macrolide antibiotics in subjects with stable COPD is consistent with anti-inflammatory properties, and macrolides should be considered as a potential therapy in COPD. Safety concerns regarding antibiotic resistance need to be addressed before widespread use in clinical practice. Copyright © 2018 by Daedalus Enterprises.

Antibiotics and antibiotic resistance in agroecosystems: State of the science

USDA-ARS?s Scientific Manuscript database

We propose a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of natural ecosystems, and agricultural productivity. Available evidence for each causal link is briefly su...

Urine Antibiotic Activity in Patients Presenting to Hospitals in Laos: Implications for Worsening Antibiotic Resistance

PubMed Central

Khennavong, Manisone; Davone, Viengmon; Vongsouvath, Manivanh; Phetsouvanh, Rattanaphone; Silisouk, Joy; Rattana, Olay; Mayxay, Mayfong; Castonguay-Vanier, Josée; Moore, Catrin E.; Strobel, Michel; Newton, Paul N.

2011-01-01

Widespread use of antibiotics may be important in the spread of antimicrobial resistance. We estimated the proportion of Lao in- and outpatients who had taken antibiotics before medical consultation by detecting antibiotic activity in their urine added to lawns of Bacillus stearothermophilus, Escherichia coli, and Streptococcus pyogenes. In the retrospective (N = 2,058) and prospective studies (N = 1,153), 49.7% (95% confidence interval [CI] = 47.4–52.0) and 36.2% (95% CI = 33.4–38.9), respectively, of Vientiane patients had urinary antibiotic activity detected. The highest frequency of estimated antibiotic pre-treatment was found in patients recruited with suspected central nervous system infections and community-acquired septicemia (both 56.8%). In Vientiane, children had a higher frequency of estimated antibiotic pre-treatment than adults (60.0% versus 46.5%; P < 0.001). Antibiotic use based on patients histories was significantly less frequent than when estimated from urinary antibiotic activity (P < 0.0001). PMID:21813851

Antibiotic use and microbiome function.

PubMed

Ferrer, Manuel; Méndez-García, Celia; Rojo, David; Barbas, Coral; Moya, Andrés

2017-06-15

Our microbiome should be understood as one of the most complex components of the human body. The use of β-lactam antibiotics is one of the microbiome covariates that influence its composition. The extent to which our microbiota changes after an antibiotic intervention depends not only on the chemical nature of the antibiotic or cocktail of antibiotics used to treat specific infections, but also on the type of administration, duration and dose, as well as the level of resistance that each microbiota develops. We have begun to appreciate that not all bacteria within our microbiota are vulnerable or reactive to different antibiotic interventions, and that their influence on both microbial composition and metabolism may differ. Antibiotics are being used worldwide on a huge scale and the prescription of antibiotics is continuing to rise; however, their effects on our microbiota have been reported for only a limited number of them. This article presents a critical review of the antibiotics or antibiotic cocktails whose use in humans has been linked to changes in the composition of our microbial communities, with a particular focus on the gut, oral, respiratory, skin and vaginal microbiota, and on their molecular agents (genes, proteins and metabolites). We review the state of the art as of June 2016, and cover a total of circa 68 different antibiotics. The data herein are the first to compile information about the bacteria, fungi, archaea and viruses most influenced by the main antibiotic treatments prescribed nowadays. Copyright © 2016 Elsevier Inc. All rights reserved.

Combating Antibiotic Resistance

MedlinePlus

... and improved tests for infectious diseases. Antibiotics Fight Bacteria, Not Viruses Antibiotics are meant to be used ... treat strep throat, which is caused by streptococcal bacteria, and skin infections caused by staphylococcal bacteria. Although ...

Targeting Antibiotic Resistance

PubMed Central

Chellat, Mathieu F.; Raguž, Luka

2016-01-01

Abstract Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens. PMID:27000559

Probiotic approach to prevent antibiotic resistance.

PubMed

Ouwehand, Arthur C; Forssten, Sofia; Hibberd, Ashley A; Lyra, Anna; Stahl, Buffy

2016-01-01

Probiotics are live microorganisms, mainly belonging to the genera Lactobacillus and Bifidobacterium, although also strain of other species are commercialized, that have a beneficial effect on the host. From the perspective of antibiotic use, probiotics have been observed to reduce the risk of certain infectious disease such as certain types of diarrhea and respiratory tract infection. This may be accompanied with a reduced need of antibiotics for secondary infections. Antibiotics tend to be effective against most common diseases, but increasingly resistance is being observed among pathogens. Probiotics are specifically selected to not contribute to the spread of antibiotic resistance and not carry transferable antibiotic resistance. Concomitant use of probiotics with antibiotics has been observed to reduce the incidence, duration and/or severity of antibiotic-associated diarrhea. This contributes to better adherence to the antibiotic prescription and thereby reduces the evolution of resistance. To what extent probiotics directly reduce the spread of antibiotic resistance is still much under investigation; but maintaining a balanced microbiota during antibiotic use may certainly provide opportunities for reducing the spread of resistances. Key messages Probiotics may reduce the risk for certain infectious diseases and thereby reduce the need for antibiotics. Probiotics may reduce the risk for antibiotic-associated diarrhea Probiotics do not contribute to the spread of antibiotic resistance and may even reduce it.

Antibiotic drug advertising in medical journals.

PubMed

Gilad, Jacob; Moran, Lia; Schlaeffer, Francisc; Borer, Abraham

2005-01-01

Advertising is a leading strategy for drug promotion. We analysed 779 advertisements in 24 medical journals, 25% of which featured antibiotics. Antibiotic advertisements showed differences compared to those of other drugs. None addressed the issue of antibiotic resistance. Efforts to prevent antibiotic resistance should take antibiotic advertising into consideration.

Effects of temperature and antibiotics on persistence of antibiotic-resistant bacteria and antibiotic resistance genes in poultry litter

USDA-ARS?s Scientific Manuscript database

The effect of low, residual concentrations of antibiotics in manure and other environmental matrices is not well understood. It has been hypothesized that antibiotic concentrations below clinical MIC (minimal inhibitory concentrations) are still capable of selecting for resistance. The objective of ...

Antibiotics produced by Streptomyces.

PubMed

Procópio, Rudi Emerson de Lima; Silva, Ingrid Reis da; Martins, Mayra Kassawara; Azevedo, João Lúcio de; Araújo, Janete Magali de

2012-01-01

Streptomyces is a genus of Gram-positive bacteria that grows in various environments, and its shape resembles filamentous fungi. The morphological differentiation of Streptomyces involves the formation of a layer of hyphae that can differentiate into a chain of spores. The most interesting property of Streptomyces is the ability to produce bioactive secondary metabolites, such as antifungals, antivirals, antitumorals, anti-hypertensives, immunosuppressants, and especially antibiotics. The production of most antibiotics is species specific, and these secondary metabolites are important for Streptomyces species in order to compete with other microorganisms that come in contact, even within the same genre. Despite the success of the discovery of antibiotics, and advances in the techniques of their production, infectious diseases still remain the second leading cause of death worldwide, and bacterial infections cause approximately 17 million deaths annually, affecting mainly children and the elderly. Self-medication and overuse of antibiotics is another important factor that contributes to resistance, reducing the lifetime of the antibiotic, thus causing the constant need for research and development of new antibiotics. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

Systems, not pills: The options market for antibiotics seeks to rejuvenate the antibiotic pipeline.

PubMed

Brogan, David M; Mossialos, Elias

2016-02-01

Over the past decade, there has been a growing recognition of the increasing growth of antibiotic resistant bacteria and a relative decline in the production of novel antibacterial therapies. The combination of these two forces poses a potentially grave threat to global health, in both developed and developing countries. Current market forces do not provide appropriate incentives to stimulate new antibiotic development, thus we propose a new incentive mechanism: the Options Market for Antibiotics. This mechanism, modelled on the principle of financial call options, allows payers to buy the right, in early stages of development, to purchase antibiotics at a discounted price if and when they ever make it to market approval. This paper demonstrates the effect of such a model on the expected Net Present Value of a typical antibacterial project. As part of an integrated strategy to confront the impending antibiotic crisis, the Options Market for Antibiotics may effectively stimulate corporate and public investment into antibiotic research and development. Copyright © 2016. Published by Elsevier Ltd.

The Comprehensive Antibiotic Resistance Database

PubMed Central

McArthur, Andrew G.; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A.; Baylay, Alison J.; Bhullar, Kirandeep; Canova, Marc J.; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M.; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R.; O'Brien, Jonathan S.; Pawlowski, Andrew C.; Piddock, Laura J. V.; Spanogiannopoulos, Peter; Sutherland, Arlene D.; Tang, Irene; Taylor, Patricia L.; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison

2013-01-01

The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175

New business models for antibiotic innovation.

PubMed

So, Anthony D; Shah, Tejen A

2014-05-01

The increase in antibiotic resistance and the dearth of novel antibiotics have become a growing concern among policy-makers. A combination of financial, scientific, and regulatory challenges poses barriers to antibiotic innovation. However, each of these three challenges provides an opportunity to develop pathways for new business models to bring novel antibiotics to market. Pull-incentives that pay for the outputs of research and development (R&D) and push-incentives that pay for the inputs of R&D can be used to increase innovation for antibiotics. Financial incentives might be structured to promote delinkage of a company's return on investment from revenues of antibiotics. This delinkage strategy might not only increase innovation, but also reinforce rational use of antibiotics. Regulatory approval, however, should not and need not compromise safety and efficacy standards to bring antibiotics with novel mechanisms of action to market. Instead regulatory agencies could encourage development of companion diagnostics, test antibiotic combinations in parallel, and pool and make transparent clinical trial data to lower R&D costs. A tax on non-human use of antibiotics might also create a disincentive for non-therapeutic use of these drugs. Finally, the new business model for antibiotic innovation should apply the 3Rs strategy for encouraging collaborative approaches to R&D in innovating novel antibiotics: sharing resources, risks, and rewards.

A modified method for measuring antibiotic use in healthcare settings: implications for antibiotic stewardship and benchmarking.

PubMed

Aldeyab, Mamoon A; McElnay, James C; Scott, Michael G; Lattyak, William J; Darwish Elhajji, Feras W; Aldiab, Motasem A; Magee, Fidelma A; Conlon, Geraldine; Kearney, Mary P

2014-04-01

To determine whether adjusting the denominator of the common hospital antibiotic use measurement unit (defined daily doses/100 bed-days) by including age-adjusted comorbidity score (100 bed-days/age-adjusted comorbidity score) would result in more accurate and meaningful assessment of hospital antibiotic use. The association between the monthly sum of age-adjusted comorbidity and monthly antibiotic use was measured using time-series analysis (January 2008 to June 2012). For the purposes of conducting internal benchmarking, two antibiotic usage datasets were constructed, i.e. 2004-07 (first study period) and 2008-11 (second study period). Monthly antibiotic use was normalized per 100 bed-days and per 100 bed-days/age-adjusted comorbidity score. Results showed that antibiotic use had significant positive relationships with the sum of age-adjusted comorbidity score (P = 0.0004). The results also showed that there was a negative relationship between antibiotic use and (i) alcohol-based hand rub use (P = 0.0370) and (ii) clinical pharmacist activity (P = 0.0031). Normalizing antibiotic use per 100 bed-days contributed to a comparative usage rate of 1.31, i.e. the average antibiotic use during the second period was 31% higher than during the first period. However, normalizing antibiotic use per 100 bed-days per age-adjusted comorbidity score resulted in a comparative usage rate of 0.98, i.e. the average antibiotic use was 2% lower in the second study period. Importantly, the latter comparative usage rate is independent of differences in patient density and case mix characteristics between the two studied populations. The proposed modified antibiotic measure provides an innovative approach to compare variations in antibiotic prescribing while taking account of patient case mix effects.

Antibiotic-Resistant Bacteria.

ERIC Educational Resources Information Center

Longenecker, Nevin E.; Oppenheimer, Dan

1982-01-01

A study conducted by high school advanced bacteriology students appears to confirm the hypothesis that the incremental administration of antibiotics on several species of bacteria (Escherichia coli, Staphylococcus epidermis, Bacillus sublitus, Bacillus megaterium) will allow for the development of antibiotic-resistant strains. (PEB)

Surveillance of life-long antibiotics: a review of antibiotic prescribing practices in an Australian Healthcare Network.

PubMed

Lau, Jillian S Y; Kiss, Christopher; Roberts, Erika; Horne, Kylie; Korman, Tony M; Woolley, Ian

2017-01-18

The rise of antimicrobial use in the twentieth century has significantly reduced morbidity due to infection, however it has also brought with it the rise of increasing resistance. Some patients are on prolonged, if not "life-long" course of antibiotics. The reasons for this are varied, and include non-infectious indications. We aimed to study the characteristics of this potential source of antibiotic resistance, by exploring the antibiotic dispensing practices and describing the population of patients on long-term antibiotic therapy. A retrospective cross-sectional study of antibiotic dispensing records was performed at a large university hospital-based healthcare network in Melbourne, Australia. Outpatient prescriptions were extracted from the hospital pharmacy database over a 6 month period in 2014. Medical records of these patients were reviewed to determine the indication for prescription, including microbiology, the intended duration, and the prescribing unit. A descriptive analysis was performed on this data. 66,127 dispensing episodes were reviewed. 202 patients were found to have been prescribed 1 or more antibiotics with an intended duration of 1 year or longer. 69/202 (34%) of these patients were prescribed prolonged antibiotics for primary prophylaxis in the setting of immunosuppression. 43/202 (21%) patients were prescribed long-term suppressive antibiotics for infections of thought incurable (e.g. vascular graft infections), and 34/43 (79%) were prescribed by Infectious Diseases doctors. 66/202 (33%) patients with cystic fibrosis were prescribed prolonged courses of macrolides or fluoroquinolones, by respiratory physicians. There was great heterogeneity noted in indications for prolonged antibiotic courses, as well as antibiotic agents utilised. Our study found that that continuous antibiotic therapy represented only a small proportion of overall antibiotic prescribing at our health network. Prolonged courses of antibiotics were used mainly to

The determinants of the antibiotic resistance process.

PubMed

Franco, Beatriz Espinosa; Altagracia Martínez, Marina; Sánchez Rodríguez, Martha A; Wertheimer, Albert I

2009-01-01

The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community. To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem. We conducted a MedLine search using the key words "determinants", "antibiotic", and "antibiotic resistance" to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded. The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance. Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals.

Antibiotics, Bacteria, and Antibiotic Resistance Genes: Aerial Transport from Cattle Feed Yards via Particulate Matter

PubMed Central

McEachran, Andrew D.; Blackwell, Brett R.; Hanson, J. Delton; Wooten, Kimberly J.; Mayer, Gregory D.; Cox, Stephen B.

2015-01-01

Background: Emergence and spread of antibiotic resistance has become a global health threat and is often linked with overuse and misuse of clinical and veterinary chemotherapeutic agents. Modern industrial-scale animal feeding operations rely extensively on veterinary pharmaceuticals, including antibiotics, to augment animal growth. Following excretion, antibiotics are transported through the environment via runoff, leaching, and land application of manure; however, airborne transport from feed yards has not been characterized. Objectives: The goal of this study was to determine the extent to which antibiotics, antibiotic resistance genes (ARG), and ruminant-associated microbes are aerially dispersed via particulate matter (PM) derived from large-scale beef cattle feed yards. Methods: PM was collected downwind and upwind of 10 beef cattle feed yards. After extraction from PM, five veterinary antibiotics were quantified via high-performance liquid chromatography with tandem mass spectrometry, ARG were quantified via targeted quantitative polymerase chain reaction, and microbial community diversity was analyzed via 16S rRNA amplification and sequencing. Results: Airborne PM derived from feed yards facilitated dispersal of several veterinary antibiotics, as well as microbial communities containing ARG. Concentrations of several antibiotics in airborne PM immediately downwind of feed yards ranged from 0.5 to 4.6 μg/g of PM. Microbial communities of PM collected downwind of feed yards were enriched with ruminant-associated taxa and were distinct when compared to upwind PM assemblages. Furthermore, genes encoding resistance to tetracycline antibiotics were significantly more abundant in PM collected downwind of feed yards as compared to upwind. Conclusions: Wind-dispersed PM from feed yards harbors antibiotics, bacteria, and ARGs. Citation: McEachran AD, Blackwell BR, Hanson JD, Wooten KJ, Mayer GD, Cox SB, Smith PN. 2015. Antibiotics, bacteria, and antibiotic

Efforts to slacken antibiotic resistance: Labeling meat products from animals raised without antibiotics in the United States.

PubMed

Centner, Terence J

2016-09-01

As bacteria and diseases spread due to climatic change, greater amounts of antibiotics will be used thereby exacerbating the problem of antibiotic resistance. To help slacken the development of resistant bacteria, the medical community is attempting to reduce unnecessary and excessive usage of antibiotics. One of the targets is the use of antibiotics for enhancing animal growth and promoting feed efficiency in the production of food animals. While governments can adopt regulations prohibiting nontherapeutic uses of antibiotics in food animals and strategies to reduce antibiotic usage, another idea is to publicize when antibiotics are used in food animal production by allowing labeled meat products. This paper builds upon existing labeling and marketing efforts in the United States to show how a government can develop a verified antibiotic-free labeling program that would allow consumers to purchase meat products from animals that had never received antibiotics. Copyright © 2016 Elsevier B.V. All rights reserved.

[Usage of antibiotics in hospitals].

PubMed

Ternák, G; Almási, I

1996-12-29

The authors publish the results of a survey conducted among hospital records of patients discharged from eight inpatient's institutes between 1-31st of January 1995 to gather information on the indications and usage of antibiotics. The institutes were selected from different part of the country to represent the hospital structure as much as possible. Data from the 13,719 documents were recorded and analysed by computer program. It was found that 27.6% of the patients (3749 cases) received antibiotic treatment. 407 different diagnosis and 365 different surgical procedures (as profilaxis) were considered as indications of antibiotic treatment (total: 4450 indications for 5849 antibiotic treatment). The largest group of patients receiving antibiotics was of antibiotic profilaxis (24.56%, 1093 cases), followed by lower respiratory tract infections (19.89%, 849 cases), uroinfections (10.53%, 469 cases) and upper respiratory tract infections. Relatively large group of patients belonged to those who had fever or subfebrility without known reason (7.35%, 327 cases) and to those who did not have any proof in their document indicating the reasons of antibiotic treatment (6.4%, 285 cases). We can not consider the antibiotic indications well founded in those groups of patients (every sixth or every fifth cases). The most frequently used antibiotics were of [2-nd] generation cefalosporins. The rate of nosocomial infections were found as 6.78% average. The results are demonstrated on diagrams and table.

Antibiotics in late clinical development.

PubMed

Fernandes, Prabhavathi; Martens, Evan

2017-06-01

Most pharmaceutical companies have stopped or have severely limited investments to discover and develop new antibiotics to treat the increasing prevalence of infections caused by multi-drug resistant bacteria, because the return on investment has been mostly negative for antibiotics that received marketing approved in the last few decades. In contrast, a few small companies have taken on this challenge and are developing new antibiotics. This review describes those antibiotics in late-stage clinical development. Most of them belong to existing antibiotic classes and a few with a narrow spectrum of activity are novel compounds directed against novel targets. The reasons for some of the past failures to find new molecules and a path forward to help attract investments to fund discovery of new antibiotics are described. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The determinants of the antibiotic resistance process

PubMed Central

Franco, Beatriz Espinosa; Altagracia Martínez, Marina; Sánchez Rodríguez, Martha A; Wertheimer, Albert I

2009-01-01

Background: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community. Objectives: To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem. Methods: We conducted a MedLine search using the key words “determinants”, “antibiotic”, and “antibiotic resistance” to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded. Results: The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance. Conclusions: Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals. PMID:21694883

The double life of antibiotics.

PubMed

Yap, Mee-Ngan F

2013-01-01

Antibiotic resistance is a persistent health care problem worldwide. Evidence for the negative consequences of subtherapeutic feeding in livestock production has been mounting while the antibiotic pipeline is drying up. In recent years, there has been a paradigm shift in our perception of antibiotics. Apart from its roles in self-defense, antibiotics also serve as inter-microbial signaling molecules, regulators of gene expression, microbial food sources, and as mediators of host immune response.

CONSORT: May stereotactic intracavity administration of antibiotics shorten the course of systemic antibiotic therapy for brain abscesses?

PubMed

Yu, Xin; Liu, Rui; Wang, Yaming; Zhao, Hulin; Chen, Jinhui; Zhang, Jianning; Hu, Chenhao

2017-05-01

Despite advances in surgical techniques in the management of the brain abscess, continuous systemic long-term antibiotics are necessary and crucial. This study was designed to evaluate the effect of intracavity administration of high-dose antibiotics on the course of antibiotic therapy. Between 2003 and 2013, 55 patients with bacterial brain abscesses (83 abscesses) were treated with stereotactic aspiration and intracavity injection of high-dose antibiotics combined with a short course systemic antibiotic therapy. Antibiotics of one-eighth daily systemic dosage were injected into the abscess cavity after stereotactic aspiration and intravenous antibiotics were given in all patients for 3 to 4 weeks. The results of the group treated with stereotactic aspiration and intracavity injection of antibiotic solution were compared to the results of our previous patients treated by stereotactic aspiration only. Thirty-nine males and 16 females (age ranging from 1.5 to 76 years; mean age 38.7 years) were included in this study. During the follow-up (mean 26.2 months, ranging from 6 to 72 months), all the abscesses subsided with no recurrence. No adverse effects related to topical use of antibiotics occurred. At the end of follow-up, 38 patients had good outcomes, 11 had mild neurological deficits, 3 had moderate deficits, 1 was in vegetative state, and 2 died of accidents not related to brain abscesses. Compared with conventional stereotactic aspiration and drainage, intracavity injection of antibiotics shorted the course of consecutive systemic intravenous antibiotics by average 10.8 days without an increase of the recurrence rate of abscesses. Our results indicate that topical application of antibiotics into the brain abscess cavity helps to reduce the length of systemic antibiotic therapy, decreases the abscess recurrence rate, avoids the side effects of long-term high dose antibiotics, shortens the hospitalization and reduces treatment costs.

Antibiotic prophylaxis in obstetric procedures.

PubMed

van Schalkwyk, Julie; Van Eyk, Nancy

2010-09-01

To review the evidence and provide recommendations on antibiotic prophylaxis for obstetrical procedures. Outcomes evaluated include need and effectiveness of antibiotics to prevent infections in obstetrical procedures. Published literature was retrieved through searches of Medline and The Cochrane Library on the topic of antibiotic prophylaxis in obstetrical procedures. Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and articles published from January 1978 to June 2009 were incorporated in the guideline. Current guidelines published by the American College of Obstetrics and Gynecology were also incorporated. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care (Table 1). Implementation of this guideline should reduce the cost and harm resulting from the administration of antibiotics when they are not required and the harm resulting from failure to administer antibiotics when they would be beneficial. SUMMARY STATEMENTS: 1. Available evidence does not support the use of prophylactic antibiotics to reduce infectious morbidity following operative vaginal delivery. (II-1) 2. There is insufficient evidence to argue for or against the use of prophylactic antibiotics to reduce infectious morbidity for manual removal of the placenta. (III) 3. There is insufficient evidence to argue for or against the use of

In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and polymethylmethacrylate beads.

PubMed Central

Mader, J T; Calhoun, J; Cobos, J

1997-01-01

Antibiotic-impregnated beads are used in the dead bone space following debridement surgery to deliver local, high concentrations of antibiotics. Polymethylmethacrylate (PMMA), 2,000-molecular-weight (MW) polylactic acid (PLA), Poly(DL-lactide)-coglycolide (PL:CG; 90:10, 80:20, and 70:30), and the combination 2,000-MW PLA-70:20 PL:CG were individually mixed with clindamycin, tobramycin, or vancomycin. Beads were placed in 1 ml of phosphate-buffered saline (PBS) and incubated at 37 degrees C. The PBS was changed daily, and the removed PBS samples were stored at -70 degrees C until the antibiotic in each sample was determined by microbiological disk diffusion assay. Nondissolving PMMA beads with tobramycin and clindamycin had concentrations well above breakpoint sensitivity concentrations (i.e., the antibiotic concentrations at the transition point between bacterial killing and resistance to the antibiotic) for more than 90 days, but vancomycin concentrations dropped by day 12. ALl PLA, PL:CG, and the 2,000-MW PLA-70:30 PL:CG biodegradable beads release high concentrations of all the antibiotics in vitro for the period of time needed to treat bone infections (i.e., 4 to 8 weeks). Antibiotic-loaded PLA and PL:CG beads have the advantage of better antibiotic elution and the ability to biodegradable (thereby averting the need for secondary surgery for bead removal) compared to the PMMA beads presently used in the clinical setting. PMID:9021200

Magnitude of antibiotic use.

PubMed

Finkel, M J

1978-11-01

Trends in antibiotic prescribing can be examined by a review of data from dispensed prescriptions and from antibiotic certification records of the Food and Drug Administration (FDA). Prescription data on selected oral antibiotics and anti-infectives were obtained from IMS America's National Prescription Audit. Data compiled between 1965 and 1977 show increasing use until 1973--with a plateau thereafter--for antibiotics judged by physicians to be relatively "safe," namely, the erythromycins, ampicillin and other penicillins, and the cephalosporins. Tetracycline use, although rising until 1973, declined somewhat thereafter, perhaps because of increasing concern with dental staining in children. Sulfonamide use has declined steadily since 1965, presumably for safety reasons. Used of clindamycin was nearing a level similar to that of cephalosporin use until 1975, when its risk of precipitating severe colitis, including pseudomembranous colitis, became well-known. The FDA's antibiotic certification records show that the volume of injectable cephalosporins and gentamicin administered has increased steadily and as of 1977 was still rising.

Antibiotics for sore throat.

PubMed

Spinks, Anneliese; Glasziou, Paul P; Del Mar, Chris B

2013-11-05

Sore throat is a common reason for people to present for medical care. Although it remits spontaneously, primary care doctors commonly prescribe antibiotics for it. To assess the benefits of antibiotics for sore throat for patients in primary care settings. We searched CENTRAL 2013, Issue 6, MEDLINE (January 1966 to July week 1, 2013) and EMBASE (January 1990 to July 2013). Randomised controlled trials (RCTs) or quasi-RCTs of antibiotics versus control assessing typical sore throat symptoms or complications. Two review authors independently screened studies for inclusion and extracted data. We resolved differences in opinion by discussion. We contacted trial authors from three studies for additional information. We included 27 trials with 12,835 cases of sore throat. We did not identify any new trials in this 2013 update. 1. Symptoms Throat soreness and fever were reduced by about half by using antibiotics. The greatest difference was seen at day three. The number needed to treat to benefit (NNTB) to prevent one sore throat at day three was less than six; at week one it was 21. 2. Non-suppurative complications The trend was antibiotics protecting against acute glomerulonephritis but there were too few cases to be sure. Several studies found antibiotics reduced acute rheumatic fever by more than two-thirds within one month (risk ratio (RR) 0.27; 95% confidence interval (CI) 0.12 to 0.60). 3. Suppurative complications Antibiotics reduced the incidence of acute otitis media within 14 days (RR 0.30; 95% CI 0.15 to 0.58); acute sinusitis within 14 days (RR 0.48; 95% CI 0.08 to 2.76); and quinsy within two months (RR 0.15; 95% CI 0.05 to 0.47) compared to those taking placebo. 4. Subgroup analyses of symptom reduction Antibiotics were more effective against symptoms at day three (RR 0.58; 95% CI 0.48 to 0.71) if throat swabs were positive for Streptococcus, compared to RR 0.78; 95% CI 0.63 to 0.97 if negative. Similarly at week one the RR was 0.29 (95% CI 0.12 to 0

More Antisepsis, Less Antibiotics Whenever Possible.

PubMed

Grzybowski, Andrzej; Turczynowska, Magdalena

2018-01-01

Increasing bacterial resistance to antibiotics has recently become an important medical challenge. In ophthalmology antibiotics are widely used for treatment and prophylaxis of ocular infections. In many cases antiseptics may be a valuable adjunct and sometimes even an alternative to antibiotics for the prevention and treatment of infections, reducing the overuse of antibiotics. This review aims to highlight the available literature on the subject of antibiotic resistance in ophthalmology. Full understanding of this growing problem is necessary for tailoring effective pre-, intra-, and postoperative management to improve antibiotic stewardship programs. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Antibiotic-Releasing Porous Polymethylmethacrylate/Gelatin/Antibiotic Constructs for Craniofacial Tissue Engineering

PubMed Central

Shi, Meng; Kretlow, James D.; Spicer, Patrick P.; Tabata, Yasuhiko; Demian, Nagi; Wong, Mark E.; Kasper, F. Kurtis; Mikos, Antonios G.

2011-01-01

An antibiotic-releasing porous polymethylmethacrylate (PMMA) construct was developed to maintain the bony space and prime the wound site in the initial step of a two-stage regenerative medicine approach toward reconstructing significant bony or composite craniofacial tissue defects. Porous polymethylmethacrylate (PMMA) constructs incorporating gelatin microparticles (GMPs) were fabricated by the sequential assembly of GMPs, the antibiotic colistin, and a clinically used bone cement formulation of PMMA powder and methylmethacrylate liquid. PMMA/gelatin/antibiotic constructs with varying gelatin incorporation and drug content were investigated to elucidate the relationship between material composition and construct properties (porosity and drug release kinetics). The porosity of PMMA/gelatin/antibiotic constructs ranged between 7.6±1.8–38.4±1.4% depending on the amount of gelatin incorporated and the drug solution added for gelatin swelling. The constructs released colistin over 10 or 14 days with an average release rate per day above 10 µg/ml. The porosity and in vitro colistin release kinetics of PMMA/gelatin/antibiotic constructs were tuned by varying the material composition and fabrication parameters. This study demonstrates the potential of gelatin-incorporating PMMA constructs as a functional space maintainer for both promoting tissue healing/coverage and addressing local infections, enabling better long-term success of the definitive regenerated tissue construct. PMID:21295086

Antibiotic resistance increases with local temperature

NASA Astrophysics Data System (ADS)

MacFadden, Derek R.; McGough, Sarah F.; Fisman, David; Santillana, Mauricio; Brownstein, John S.

2018-06-01

Bacteria that cause infections in humans can develop or acquire resistance to antibiotics commonly used against them1,2. Antimicrobial resistance (in bacteria and other microbes) causes significant morbidity worldwide, and some estimates indicate the attributable mortality could reach up to 10 million by 20502-4. Antibiotic resistance in bacteria is believed to develop largely under the selective pressure of antibiotic use; however, other factors may contribute to population level increases in antibiotic resistance1,2. We explored the role of climate (temperature) and additional factors on the distribution of antibiotic resistance across the United States, and here we show that increasing local temperature as well as population density are associated with increasing antibiotic resistance (percent resistant) in common pathogens. We found that an increase in temperature of 10 °C across regions was associated with an increases in antibiotic resistance of 4.2%, 2.2%, and 2.7% for the common pathogens Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The associations between temperature and antibiotic resistance in this ecological study are consistent across most classes of antibiotics and pathogens and may be strengthening over time. These findings suggest that current forecasts of the burden of antibiotic resistance could be significant underestimates in the face of a growing population and climate change4.

Empirical use of antibiotics and adjustment of empirical antibiotic therapies in a university hospital: a prospective observational study

PubMed Central

Mettler, Julian; Simcock, Mathew; Sendi, Pedram; Widmer, Andreas F; Bingisser, Roland; Battegay, Manuel; Fluckiger, Ursula; Bassetti, Stefano

2007-01-01

Background Several strategies to optimise the use of antibiotics have been developed. Most of these interventions can be classified as educational or restrictive. Restrictive measures are considered to be more effective, but the enforcement of these measures may be difficult and lead to conflicts with prescribers. Any intervention should be aimed at targets with the highest impact on antibiotic prescribing. The aim of the present study was to assess the adequacy of empirical and adjusted antibiotic therapies in a Swiss university hospital where no antibiotic use restrictions are enforced, and to identify risk factors for inadequate treatment and targets for intervention. Methods A prospective observational study was performed during 9 months. All patients admitted through the emergency department who received an antibiotic therapy within 24 hours of admission were included. Data on demographic characteristics, diagnoses, comorbidities, systemic inflammatory response syndrome (SIRS) parameters, microbiological tests, and administered antibiotics were collected prospectively. Antibiotic therapy was considered adequate if spectrum, dose, application modus, and duration of therapy were appropriate according to local recommendations or published guidelines. Results 2943 admitted patients were evaluated. Of these, 572 (19.4%) received antibiotics within 24 hours and 539 (94%) were analysed in detail. Empirical antibiotic therapy was inadequate in 121 patients (22%). Initial therapy was adjusted in 168 patients (31%). This adjusted antibiotic therapy was inadequate in 46 patients (27%). The main reason for inadequacy was the use of antibiotics with unnecessarily broad spectrum (24% of inadequate empirical, and 52% of inadequate adjusted therapies). In 26% of patients with inadequate adjusted therapy, antibiotics used were either ineffective against isolated pathogenic bacteria or antibiotic therapy was continued despite negative results of microbiological investigations

Synthetic membrane-targeted antibiotics.

PubMed

Vooturi, S K; Firestine, S M

2010-01-01

Antimicrobial resistance continues to evolve and presents serious challenges in the therapy of both nosocomial and community-acquired infections. The rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant enterococci (VRE) suggests that antimicrobial resistance is an inevitable evolutionary response to antimicrobial use. This highlights the tremendous need for antibiotics against new bacterial targets. Agents that target the integrity of bacterial membrane are relatively novel in the clinical armamentarium. Daptomycin, a lipopeptide is a classical example of membrane-bound antibiotic. Nature has also utilized this tactic. Antimicrobial peptides (AMPs), which are found in all kingdoms, function primarily by permeabilizing the bacterial membrane. AMPs have several advantages over existing antibiotics including a broad spectrum of activity, rapid bactericidal activity, no cross-resistance with the existing antibiotics and a low probability for developing resistance. Currently, a small number of peptides have been developed for clinical use but therapeutic applications are limited because of poor bioavailability and high manufacturing cost. However, their broad specificity, potent activity and lower probability for resistance have spurred the search for synthetic mimetics of antimicrobial peptides as membrane-active antibiotics. In this review, we will discuss the different classes of synthetic membrane-bound antibiotics published since 2004.

Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

EPA Science Inventory

Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

Grievances in cases using antibiotics due to orodental problems and assessment of the need for antibiotics.

PubMed

Kandemir, S; Ergül, N

2000-04-01

To assess the complaints of patients who were prescribed antibiotics following orodental problems and the need for antibiotics prescribed for this purpose. Examinations were carried out in the Department of Oral Diagnosis and Radiology, Ege University, Turkey. A total of 203 patients (129 females and 74 males) between 8-70 years of age (mean age 37.7 +/- 13.9). Examination and report. Frequency of unnecessary antibiotic use. Antibiotic therapy was not necessary for 151 (74.4 per cent) cases. Antibiotics were unnecessarily prescribed in 45 cases of acute irreversible pulpitis, 10 chronic apical abscess, 6 acute apical paradontitis, 7 gingivitis, 10 periodontitis, 4 epulis, 2 TMJ (temporomandibular junction) dysfunction, 2 sharp ridge of alveolar bone, 1 burning mouth syndrome and 1 recurrent aphthous stomatitis. In 108 (53.2 per cent) of the cases, the prescribed antibiotics were found to be penicillins, 102 of which were broad-spectrum. It was also determined that only 6 (7.7 per cent) of the 78 cases diagnosed as acute apical abscess were given drainage as local therapy. Principles for treating dental infections suggest that an antibiotic should only be used to supplement and not substitute for conventional surgical methods. Therefore, in cases with acute apical abscess, mechanical treatment (drainage) should be the first step. Inappropriate antibiotic use is quite widespread in dentistry. Dentists should avoid inappropriate use of antibiotics. To prevent inappropriate administration, necessary precautions need to be taken against dispensing antibiotics without prescription.

Origins and Evolution of Antibiotic Resistance

PubMed Central

Davies, Julian; Davies, Dorothy

2010-01-01

Summary: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory. PMID:20805405

Investigating the Antibiotic Resistance Problem.

ERIC Educational Resources Information Center

Lawson, Michael; Lawson, Amy L.

1998-01-01

Seeks to give teachers useful information on the extent of the problem of antibiotic-resistant bacteria, mechanisms bacteria use to resist antibiotics, the causes of the emergence of antibiotic-resistant organisms, and practices that can prevent or reverse this trend. Contains 19 references. (DDR)

Changes in antibiotic concentrations and antibiotic resistome during commercial composting of animal manures.

PubMed

Xie, Wan-Ying; Yang, Xin-Ping; Li, Qian; Wu, Long-Hua; Shen, Qi-Rong; Zhao, Fang-Jie

2016-12-01

The over-use of antibiotics in animal husbandry in China and the concomitant enhanced selection of antibiotic resistance genes (ARGs) in animal manures are of serious concern. Thermophilic composting is an effective way of reducing hazards in organic wastes. However, its effectiveness in antibiotic degradation and ARG reduction in commercial operations remains unclear. In the present study, we determined the concentrations of 15 common veterinary antibiotics and the abundances of 213 ARGs and 10 marker genes for mobile genetic elements (MGEs) in commercial composts made from cattle, poultry and swine manures in Eastern China. High concentrations of fluoroquinolones were found in the poultry and swine composts, suggesting insufficient removal of these antibiotics by commercial thermophilic composting. Total ARGs in the cattle and poultry manures were as high as 1.9 and 5.5 copies per bacterial cell, respectively. After thermophilic composting, the ARG abundance in the mature compost decreased to 9.6% and 31.7% of that in the cattle and poultry manure, respectively. However, some ARGs (e.g. aadA, aadA2, qacEΔ1, tetL) and MGE marker genes (e.g. cintI-1, intI-1 and tnpA-04) were persistent with high abundance in the composts. The antibiotics that were detected at high levels in the composts (e.g. norfloxacin and ofloxacin) might have posed a selection pressure on ARGs. MGE marker genes were found to correlate closely with ARGs at the levels of individual gene, resistance class and total abundance, suggesting that MGEs and ARGs are closely associated in their persistence in the composts under antibiotic selection. Our research shows potential disseminations of antibiotics and ARGs via compost utilization. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antibiotics and inflammatory bowel diseases.

PubMed

Scribano, Maria Lia; Prantera, Cosimo

2013-01-01

Inflammatory bowel diseases are characterized by an altered composition of gut microbiota (dysbiosis) that may contribute to their development. Antibiotics can alter the bacterial flora, and a link between antibiotic use and onset of Crohn's disease (CD), but not ulcerative colitis, has been reported. The hypothesis that Mycobacterium avium subspecies paratuberculosis (MAP) could be an etiologic agent of CD has not been confirmed by a large study on patients treated by an association of antibiotics active against MAP. The observations supporting a role of intestinal microbiota in CD pathogenesis provide the rationale for a therapeutic manipulation of the intestinal flora through the employment of antibiotics. However, current data do not strongly support a therapeutic benefit from antibiotics, and there is still controversy regarding their use as primary therapy for treatment of acute flares of CD, and for postoperative recurrence prevention. Nevertheless, clinical practice and some studies suggest that a subgroup of patients with colonic involvement, early disease, and abnormal laboratory test of inflammation may respond better to antibiotic treatment. Since their long-term use is frequently complicated by a high rate of side effects, the use of antibiotics that work locally appears to be promising.

Broad-spectrum antibiotics in Norwegian hospitals.

PubMed

Holen, Øyunn; Alberg, Torunn; Blix, Hege Salvesen; Smith, Ingrid; Neteland, Marion Iren; Eriksen, Hanne Merete

2017-03-01

BACKGROUND One of the objectives in the action plan to reduce antimicrobial resistance in the health services in Norway is to reduce the use of broad-spectrum antibiotics in Norwegian hospitals. This study describes the use of certain broad-spectrum antibiotics mentioned in the action plan in Norwegian hospitals, and assesses prescribing practices in relation to the Norwegian guidelines for antibiotic use in hospitals.MATERIAL AND METHOD Data were analysed from a nationwide non-identifiable point prevalence survey in May 2016 where all systemic use of antibiotics was recorded.RESULTS Broad-spectrum antibiotics accounted for 33 % of all antibiotics prescribed. Altogether 84 % of all broad-spectrum antibiotics were prescribed as treatment, 8 % were for prophylactic use, and 8 % were classified as other/unknown. Lower respiratory tract infections were the most frequent indication for treatment with broad-spectrum antibiotics, involving 30 % of all broad-spectrum treatment.INTERPRETATION This point prevalence survey in Norwegian hospitals in spring 2016 indicates a possibility for reducing the use of broad-spectrum antibiotics in the treatment of lower respiratory tract infections and for prophylactic use. Reduction of healthcare-associated infections may also contribute.

Pipeline of Known Chemical Classes of Antibiotics

PubMed Central

d’Urso de Souza Mendes, Cristina; de Souza Antunes, Adelaide Maria

2013-01-01

Many approaches are used to discover new antibiotic compounds, one of the most widespread being the chemical modification of known antibiotics. This type of discovery has been so important in the development of new antibiotics that most antibiotics used today belong to the same chemical classes as antibiotics discovered in the 1950s and 1960s. Even though the discovery of new classes of antibiotics is urgently needed, the chemical modification of antibiotics in known classes is still widely used to discover new antibiotics, resulting in a great number of compounds in the discovery and clinical pipeline that belong to existing classes. In this scenario, the present article presents an overview of the R&D pipeline of new antibiotics in known classes of antibiotics, from discovery to clinical trial, in order to map out the technological trends in this type of antibiotic R&D, aiming to identify the chemical classes attracting most interest, their spectrum of activity, and the new subclasses under development. The result of the study shows that the new antibiotics in the pipeline belong to the following chemical classes: quinolones, aminoglycosides, macrolides, oxazolidinones, tetracyclines, pleuromutilins, beta-lactams, lipoglycopeptides, polymyxins and cyclic lipopeptides. PMID:27029317

Nucleoside antibiotics: biosynthesis, regulation, and biotechnology.

PubMed

Niu, Guoqing; Tan, Huarong

2015-02-01

The alarming rise in antibiotic-resistant pathogens has coincided with a decline in the supply of new antibiotics. It is therefore of great importance to find and create new antibiotics. Nucleoside antibiotics are a large family of natural products with diverse biological functions. Their biosynthesis is a complex process through multistep enzymatic reactions and is subject to hierarchical regulation. Genetic and biochemical studies of the biosynthetic machinery have provided the basis for pathway engineering and combinatorial biosynthesis to create new or hybrid nucleoside antibiotics. Dissection of regulatory mechanisms is leading to strategies to increase the titer of bioactive nucleoside antibiotics. Copyright © 2014. Published by Elsevier Ltd.

Magnetic Nanoparticles for Antibiotics Detection

PubMed Central

Cristea, Cecilia; Tertis, Mihaela; Galatus, Ramona

2017-01-01

Widespread use of antibiotics has led to pollution of waterways, potentially creating resistance among freshwater bacterial communities. Microorganisms resistant to commonly prescribed antibiotics (superbug) have dramatically increased over the last decades. The presence of antibiotics in waters, in food and beverages in both their un-metabolized and metabolized forms are of interest for humans. This is due to daily exposure in small quantities, that, when accumulated, could lead to development of drug resistance to antibiotics, or multiply the risk of allergic reaction. Conventional analytical methods used to quantify antibiotics are relatively expensive and generally require long analysis time associated with the difficulties to perform field analyses. In this context, electrochemical and optical based sensing devices are of interest, offering great potentials for a broad range of analytical applications. This review will focus on the application of magnetic nanoparticles in the design of different analytical methods, mainly sensors, used for the detection of antibiotics in different matrices (human fluids, the environmental, food and beverages samples). PMID:28538684

Antibiotics in Drinking Water in Shanghai and Their Contribution to Antibiotic Exposure of School Children.

PubMed

Wang, Hexing; Wang, Na; Wang, Bin; Zhao, Qi; Fang, Hong; Fu, Chaowei; Tang, Chuanxi; Jiang, Feng; Zhou, Ying; Chen, Yue; Jiang, Qingwu

2016-03-01

A variety of antibiotics have been found in aquatic environments, but antibiotics in drinking water and their contribution to antibiotic exposure in human are not well-explored. For this, representative drinking water samples and 530 urine samples from schoolchildren were selected in Shanghai, and 21 common antibiotics (five macrolides, two β-lactams, three tetracyclines, four fluoquinolones, four sulfonamides, and three phenicols) were measured in water samples and urines by isotope dilution two-dimensional ultraperformance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry. Drinking water included 46 terminal tap water samples from different spots in the distribution system of the city, 45 bottled water samples from 14 common brands, and eight barreled water samples of different brands. Of 21 antibiotics, only florfenicol and thiamphenicol were found in tap water, with the median concentrations of 0.0089 ng/mL and 0.0064 ng/mL, respectively; only florfenicol was found in three bottled water samples from a same brand, with the concentrations ranging from 0.00060 to 0.0010 ng/mL; no antibiotics were found in barreled water. In contrast, besides florfenicol and thiamphenicol, an additional 17 antibiotics were detected in urine samples, and the total daily exposure doses and detection frequencies of florfenicol and thiamphenicol based on urine samples were significantly and substantially higher than their predicted daily exposure doses and detection frequencies from drinking water by Monte Carlo Simulation. These data indicated that drinking water was contaminated by some antibiotics in Shanghai, but played a limited role in antibiotic exposure of children.

Management Options for Reducing the Release of Antibiotics and Antibiotic Resistance Genes to the Environment

PubMed Central

Pruden, Amy; Amézquita, Alejandro; Collignon, Peter; Brandt, Kristian K.; Graham, David W.; Lazorchak, James M.; Suzuki, Satoru; Silley, Peter; Snape, Jason R.; Topp, Edward; Zhang, Tong; Zhu, Yong-Guan

2013-01-01

Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. Methods: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. Discussion: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action. PMID:23735422

β-Lactam Antibiotics Renaissance

PubMed Central

Qin, Wenling; Panunzio, Mauro; Biondi, Stefano

2014-01-01

Since the 1940s β-lactam antibiotics have been used to treat bacterial infections. However, emergence and dissemination of β-lactam resistance has reached the point where many marketed β-lactams no longer are clinically effective. The increasing prevalence of multidrug-resistant bacteria and the progressive withdrawal of pharmaceutical companies from antibiotic research have evoked a strong reaction from health authorities, who have implemented initiatives to encourage the discovery of new antibacterials. Despite this gloomy scenario, several novel β-lactam antibiotics and β-lactamase inhibitors have recently progressed into clinical trials, and many more such compounds are being investigated. Here we seek to provide highlights of recent developments relating to the discovery of novel β-lactam antibiotics and β-lactamase inhibitors. PMID:27025744

Topical antibiotics: therapeutic value or ecologic mischief?

PubMed

Del Rosso, James Q; Kim, Grace K

2009-01-01

Based on antibiotic prescribing data from 2003, dermatologists account annually for 8-9 million prescriptions for oral antibiotics, and 3-4 million prescriptions for topical antibiotics. Overall, much of the emphasis on concerns related to emergence of clinically significant antibiotic-resistant bacterial strains focuses on use of systemic antibiotics, however, topical antibiotic use may also have potential implications. The following article discusses the perspectives of the authors related to the potential therapeutic benefits and ecologic implications ("ecologic mischief") of topical antibiotic therapy for specific indications encountered in ambulatory dermatology practice.

[A study of non-antibiotic versus antibiotic prophylaxis for recurrent urinary-tract infections in women (the NAPRUTI study)].

PubMed

Beerepoot, M A J; Stobberingh, E E; Geerlings, S E

2006-03-11

Patient enrolment in the 'Non-antibiotic versus antibiotic prophylaxis for recurrent urinary-tract infections' (NAPRUTI) study was started in September 2005. In this study of women with recurrent urinary-tract infections we aim to investigate the effect of 12 months of non-antibiotic prophylaxis in comparison with antibiotic prophylaxis on the rate of recurrence of urinary-tract infections and the development of antibiotic resistance. The study consists of two interlinked, randomised, clinical non-inferiority trials. In one trial, 280 premenopausal women will receive either cranberry capsules (twice daily 500 mg) or standardised antibiotic therapy (once daily 480 mg trimethoprim-sulfamethoxazole). In the other trial, 280 postmenopausal women will receive either oral lactobacilli (twice daily a capsule with > 10(9) colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14) or standardised antibiotic therapy. Non-inferiority of non-antibiotic prophylaxis would be attractive given its potential to reduce the prevalence of microbial resistance to antibiotics significantly.

The Prehistory of Antibiotic Resistance.

PubMed

Perry, Julie; Waglechner, Nicholas; Wright, Gerard

2016-06-01

Antibiotic resistance is a global problem that is reaching crisis levels. The global collection of resistance genes in clinical and environmental samples is the antibiotic "resistome," and is subject to the selective pressure of human activity. The origin of many modern resistance genes in pathogens is likely environmental bacteria, including antibiotic producing organisms that have existed for millennia. Recent work has uncovered resistance in ancient permafrost, isolated caves, and in human specimens preserved for hundreds of years. Together with bioinformatic analyses on modern-day sequences, these studies predict an ancient origin of resistance that long precedes the use of antibiotics in the clinic. Understanding the history of antibiotic resistance is important in predicting its future evolution. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

[Antibiotic Consumption and the Development of Antibiotic Resistance in Surgical Units].

PubMed

Tammer, I; Geginat, G; Lange, S; Kropf, S; Lodes, U; Schlüter, D; Lippert, H; Meyer, F

2016-02-01

Antibiotic resistence is increasing worldwide. A longitudinal analysis of the influence of the density of antibiotic use on the development of resistance in surgical units was undertaken. Over five years the incidence of pathogens and the resistance rates of isolates from patients of normal surgical units and those of a surgical ICU at a university hospital were examined. The resistence rates were correlated with the density of antibiotic use - calculated from the antibiotic consumption (in DDD) and the number of patient-days. At both units, Enterobacteriaceae and Enterococci were mostly cultured. Among the Enterobacteriaceae, E. coli, Klebsiella spp., Proteus mirabilis and Enterobacter predominated. In the group of Enterococci, E. faecalis predominated at wards whereas at ICU E. faecium was the most frequent. Anaerobes ranked third at normal wards and Candida spp. at ICU. From 2007 to 2011, there was an increasing resistance against ciprofloxacin in P. mirabilis (r = 0.87; p = 0.054) and against imipenem (r = 0.86; p = 0.06) and piperacillin (r = 0.81; p = 0.09) in P. aeruginosa at normal wards. At ICU, the resistance rates of imipenem in P. aeruginosa rose (r = 0.88; p = 0.049). Resistance against ciprofloxacin in E. coli increased (r = 0.65; p = 0.23). Due to the increasing use of ciprofloxacin and meropenem at normal wards, the density of antibiotic usage rose 1.4 %/year (r = 0.94; p = 0.02). Despite the increase of meropenem use at ICU (r = 0.9; p = 0.035), the total antibiotic uptake rate remained almost constant. The antibiotic usage density was 3-fold higher at ICU than at normal wards. At normal wards, the ciprofloxacin usage correlated with the rate of resistance against ciprofloxacin in P. mirabilis P. m. At ICU, an association was detected between the uptake rate of ceftazidime and the rate of resistance against cefotaxime in the CES group. In P. aeruginosa, the use of piperacillin and the rate

Review of Antibiotic and Non-Antibiotic Properties of Beta-lactam Molecules.

PubMed

Ochoa-Aguilar, Abraham; Ventura-Martinez, Rosa; Sotomayor-Sobrino, Marco Antonio; Gómez, Claudia; Morales-Espinoza, María del Rosario

2016-01-01

Beta-lactam molecules are a family of drugs commonly used for their antibiotic properties; however, recent research has shown that several members of this group present a large number of other effects such as neuroprotective, antioxidant, analgesic or immunomodulatory capabilities. These properties have been used in both preclinical and clinical studies in different diseases such as hypoxic neuronal damage or acute and chronic pain. The present work briefly reviews the antibiotic effect of these molecules, and will then focus specially on the non-antibiotic effects of three beta-lactam subfamilies: penicillins, cephalosporins and beta lactamase inhibitors, each of which have different molecular structure and pharmacokinetics and therefore have several potential clinical applications. A thorough search of bibliographic databases for peer-reviewed research was performed including only classic experiments or high quality reviews for the antibiotic mechanisms of beta-lactam molecules and only experimental research papers where included when the non-antibiotic properties of these molecules were searched. Only published articles from indexed journals were included. Quality of retrieved papers was assessed using standard tools. The characteristics of screened papers were described and findings of included studies were contextualized to either a mechanistic or a clinical framework. Seventy-eight papers were included in the review; the majority (56) were relative to the non-antibiotic properties of beta-lactam molecules. The non-antibiotic effects reviewed were divided accordingly to the amount of information available for each one. Twelve papers outlined the epileptogenic effects induced by beta-lactam molecules administration; these included both clinical and basic research as well as probable mechanistic explanations. Eighteen papers described a potential neuroprotective effect, mostly in basic in vitro and in vivo experiments. Analgesic properties where identified in

Antibiotic resistance rates and physician antibiotic prescription patterns of uncomplicated urinary tract infections in southern Chinese primary care

PubMed Central

Kung, Kenny; Au-Doung, Philip Lung Wai; Ip, Margaret; Lee, Nelson; Fung, Alice; Wong, Samuel Yeung Shan

2017-01-01

Uncomplicated urinary tract infections (UTI) are common in primary care. Whilst primary care physicians are called to be antimicrobial stewards, there is limited primary care antibiotic resistance surveillance and physician antibiotic prescription data available in southern Chinese primary care. The study aimed to investigate the antibiotic resistance rate and antibiotic prescription patterns in female patients with uncomplicated UTI. Factors associated with antibiotic resistance and prescription was explored. A prospective cohort study was conducted in 12 primary care group clinics in Hong Kong of patients presenting with symptoms of uncomplicated UTI from January 2012 to December 2013. Patients’ characteristics such as age, comorbidity, presenting symptoms and prior antibiotic use were recorded by physicians, as well as any empirical antibiotic prescription given at presentation. Urine samples were collected to test for antibiotic resistance of uropathogens. Univariate analysis was conducted to identify factors associated with antibiotic resistance and prescription. A total of 298 patients were included in the study. E. coli was detected in 107 (76%) out of the 141 positive urine samples. Antibiotic resistance rates of E. coli isolates for ampicillin, co-trimoxazole, ciprofloxacin, amoxicillin and nitrofurantoin were 59.8%, 31.8%, 23.4%, 1.9% and 0.9% respectively. E. coli isolates were sensitive to nitrofurantoin (98.1%) followed by amoxicillin (78.5%). The overall physician antibiotic prescription rate was 82.2%. Amoxicillin (39.6%) and nitrofurantoin (28.6%) were the most common prescribed antibiotics. Meanwhile, whilst physicians in public primary care prescribed more amoxicillin (OR: 2.84, 95% CI: 1.67 to 4.85, P<0.001) and nitrofurantoin (OR: 2.01, 95% CI: 1.14 to 3.55, P = 0.015), physicians in private clinics prescribed more cefuroxime and ciprofloxacin (P<0.05). Matching of antibiotic prescription and antibiotic sensitivity of E. coli isolates occurred

Formation of Linear Gradient of Antibiotics on Microfluidic Chips for High-throughput Antibiotic Susceptibility Testing

NASA Astrophysics Data System (ADS)

Kim, Seunggyu; Lee, Seokhun; Jeon, Jessie S.

2017-11-01

To determine the most effective antimicrobial treatments of infectious pathogen, high-throughput antibiotic susceptibility test (AST) is critically required. However, the conventional AST requires at least 16 hours to reach the minimum observable population. Therefore, we developed a microfluidic system that allows maintenance of linear antibiotic concentration and measurement of local bacterial density. Based on the Stokes-Einstein equation, the flow rate in the microchannel was optimized so that linearization was achieved within 10 minutes, taking into account the diffusion coefficient of each antibiotic in the agar gel. As a result, the minimum inhibitory concentration (MIC) of each antibiotic against P. aeruginosa could be immediately determined 6 hours after treatment of the linear antibiotic concentration. In conclusion, our system proved the efficacy of a high-throughput AST platform through MIC comparison with Clinical and Laboratory Standards Institute (CLSI) range of antibiotics. This work was supported by the Climate Change Research Hub (Grant No. N11170060) of the KAIST and by the Brain Korea 21 Plus project.

Antibiotics for acute bronchitis.

PubMed

Smith, Susan M; Fahey, Tom; Smucny, John; Becker, Lorne A

2017-06-19

The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. To assess the effects of antibiotics in improving outcomes and to assess adverse effects of antibiotic therapy for people with a clinical diagnosis of acute bronchitis. We searched CENTRAL 2016, Issue 11 (accessed 13 January 2017), MEDLINE (1966 to January week 1, 2017), Embase (1974 to 13 January 2017), and LILACS (1982 to 13 January 2017). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 5 April 2017. Randomised controlled trials comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in people without underlying pulmonary disease. At least two review authors extracted data and assessed trial quality. We did not identify any new trials for inclusion in this 2017 update. We included 17 trials with 5099 participants in the primary analysis. The quality of trials was generally good. At follow-up there was no difference in participants described as being clinically improved between the antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15). Participants given antibiotics were less likely to have a cough (4 studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) 6) and a night cough (4 studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7). Participants given antibiotics had a shorter mean cough duration (7 studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated participants were more likely to be improved according to clinician's global assessment (6 studies

The antibiotic resistome: what's new?

PubMed

Perry, Julie Ann; Westman, Erin Louise; Wright, Gerard D

2014-10-01

The antibiotic resistome is dynamic and ever expanding, yet its foundations were laid long before the introduction of antibiotics into clinical practice. Here, we revisit our theoretical framework for the resistome concept and consider the many factors that influence the evolution of novel resistance genes, the spread of mobile resistance elements, and the ramifications of these processes for clinical practice. Observing the trends and prevalence of genes within the antibiotic resistome is key to maintaining the efficacy of antibiotics in the clinic. Copyright © 2014 Elsevier Ltd. All rights reserved.

The revival of old antibiotics for treatment of uncomplicated urinary tract infections in the era of antibiotic stewardship.

PubMed

Kranz, Jennifer; Helbig, Sina; Mandraka, Falitsa; Schmidt, Stefanie; Naber, Kurt G

2017-03-01

In the era of increasing antibiotic resistance worldwide, this review highlights the advantages of revival of old antibiotics for treatment of uncomplicated urinary tract infections (uUTIs). Recent studies have shown that these four oral old antibiotics, fosfomycin trometamol, nitrofurantoin, nitroxoline and pivmecillinam, show no increasing antibiotic resistance against uropathogens causing uUTI, are still effective for the treatment of uUTI and exhibit only minimal or no collateral damage as compared with fluoroquinolones or third-generation cephalosporines. According to the principles of antibiotic stewardship, the prudent use of antibiotics is needed. Therefore, recent international and national guidelines already favour these old oral antibiotics as first-choice treatment of uUTI. Unfortunately, implementation of these guidelines is still suboptimal.

Practical Management of Antibiotic Hypersensitivity in 2017.

PubMed

Macy, Eric; Romano, Antonino; Khan, David

Antibiotics are the most common class of medications that individuals report allergy or intolerance to. Adverse reactions are reported at a predictable rate with all antibiotic use that vary by antibiotic. Antibiotic allergy incidence rates are sex dependent, higher in females than in males. Most of these events are not reproducible or immunologically mediated. Antibiotic allergy prevalence increases with increasing age and is more common in hospitalized populations and in populations that use more antibiotics. Determining potential mechanisms for the observed symptoms of the adverse reactions is the starting point for effective management of antibiotic hypersensitivity. Skin testing and direct challenges are the primary tools used to determine acute tolerance in 2017. Commercially available in vitro testing is not currently clinically useful in determining antibiotic hypersensitivity, with rare exceptions. Desensitization can be used when acute-onset immunologically mediated hypersensitivity is confirmed to safely administer a needed antibiotic. Desensitization is not possible when clinically significant T-cell-mediated delayed-type hypersensitivity is present. Effective management of antibiotic allergy is an important part of a comprehensive antibiotic stewardship program. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Antibiotics prescription in Nigerian dental healthcare services.

PubMed

Azodo, C C; Ojehanon, P I

2014-09-01

Inappropriate antibiotics prescription in dental healthcare delivery that may result in the emergence of antibiotic-resistant bacteria, is a worldwide concern. The objective of the study was to determine the antibiotics knowledge and prescription patterns among dentists in Nigeria. A total of 160 questionnaires were distributed to dentists attending continuing education courses organized by two organizations in Southern and Northern parts of Nigeria. Data analysis was done using SPSS version 17.0. A total of 146 questionnaires were returned, properly filled, out of 160 questionnaires, giving an overall response rate 91.3%. The clinical factors predominantly influenced the choice of therapeutic antibiotics among the respondents. In this study, the most commonly prescribed antibiotics among the respondents was a combination of amoxicillin and metronidazole. Of the respondents, 136 (93.2%) of them considered antibiotic resistance as a major problem in Nigeria and 102 (69.9%) have experienced antibiotics resistance in dental practice. The major reported conditions for prophylactic antibiotics among the respondents were diabetic mellitus, HIV/AIDS, history of rheumatic fever, other heart anomalies presenting with heart murmur and presence of prosthetic hip. The knowledge of adverse effects of antibiotics was greatest for tooth discoloration which is related to tetracycline. Data from this study revealed the most commonly prescribed antibiotics as a combination of amoxicillin and metronidazole. There existed gaps in prophylactic antibiotic prescription, consideration in the choice of therapeutic antibiotics and knowledge of adverse effects of antibiotics among the studied dentists.

Prophylactic antibiotics in dermatological surgery.

PubMed

Lee, Michael R; Paver, Robert

2016-05-01

This is a review of the common pathogens of surgical site infections, antibiotic coverage for particular anatomical sites, mechanisms by which surgical site infections occur and the latest data and recommendations for prophylactic antibiotics in the prevention of surgical site infections, infective endocarditis and haematogenous joint infections. Recent evidence-based guidelines on surgical prophylaxis is for restricted indications and a shorter duration of antibiotic prophylaxis in situations where no clinical benefit of prolonged therapy has been proven, in order to minimise the potential adverse ecological and clinical effects associated with antibiotic therapy. This review recommends the cautious use of prophylactic antibiotics in dermatological surgery to help prevent the growing problem of bacterial resistance as well as other morbidity and health-care costs. © 2015 The Australasian College of Dermatologists.

Antibiotics for acute bronchitis.

PubMed

Smith, Susan M; Fahey, Tom; Smucny, John; Becker, Lorne A

2014-03-01

The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. To assess the effects of antibiotics in improving outcomes and assess adverse effects of antibiotic therapy for patients with a clinical diagnosis of acute bronchitis. We searched CENTRAL 2013, Issue 12, MEDLINE (1966 to January week 1, 2014), EMBASE (1974 to January 2014) and LILACS (1982 to January 2014). Randomised controlled trials (RCTs) comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in patients without underlying pulmonary disease. At least two review authors extracted data and assessed trial quality. Seventeen trials with 3936 participants were included in the primary analysis. The quality of trials was generally good. There was limited evidence to support the use of antibiotics in acute bronchitis. At follow-up, there was no difference in participants described as being clinically improved between antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15; number needed to treat for an additional beneficial outcome (NNTB) 22. Participants given antibiotics were less likely to have a cough (four studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; NNTB 6); have a night cough (four studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7) and a shorter mean cough duration (seven studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated patients were more likely to be unimproved according to clinician's global assessment (six studies with 891 participants, RR 0.61, 95% CI 0.48 to 0.79; NNTB 25); have an abnormal lung exam (five studies with 613 participants, RR 0.54, 95% CI 0.41 to 0.70; NNTB

Induction of a stable sigma factor SigR by translation-inhibiting antibiotics confers resistance to antibiotics.

PubMed

Yoo, Ji-Sun; Oh, Gyeong-Seok; Ryoo, Sungweon; Roe, Jung-Hye

2016-06-27

Antibiotic-producing streptomycetes are rich sources of resistance mechanisms against endogenous and exogenous antibiotics. An ECF sigma factor σ(R) (SigR) is known to govern the thiol-oxidative stress response in Streptomyces coelicolor. Amplification of this response is achieved by producing an unstable isoform of σ(R) called σ(R'). In this work, we present evidence that antibiotics induce the SigR regulon via a redox-independent pathway, leading to antibiotic resistance. The translation-inhibiting antibiotics enhanced the synthesis of stable σ(R), eliciting a prolonged response. WblC/WhiB7, a WhiB-like DNA-binding protein, is responsible for inducing sigRp1 transcripts encoding the stable σ(R). The amount of WblC protein and its binding to the sigRp1 promoter in vivo increased upon antibiotic treatment. A similar phenomenon appears to exist in Mycobacterium tuberculosis as well. These findings reveal a novel antibiotic-induced resistance mechanism conserved among actinomycetes, and also give an explicit example of overlap in cellular damage and defense mechanisms between thiol-oxidative and anti- translational stresses.

Induction of a stable sigma factor SigR by translation-inhibiting antibiotics confers resistance to antibiotics

PubMed Central

Yoo, Ji-Sun; Oh, Gyeong-Seok; Ryoo, Sungweon; Roe, Jung-Hye

2016-01-01

Antibiotic-producing streptomycetes are rich sources of resistance mechanisms against endogenous and exogenous antibiotics. An ECF sigma factor σR (SigR) is known to govern the thiol-oxidative stress response in Streptomyces coelicolor. Amplification of this response is achieved by producing an unstable isoform of σR called σR′. In this work, we present evidence that antibiotics induce the SigR regulon via a redox-independent pathway, leading to antibiotic resistance. The translation-inhibiting antibiotics enhanced the synthesis of stable σR, eliciting a prolonged response. WblC/WhiB7, a WhiB-like DNA-binding protein, is responsible for inducing sigRp1 transcripts encoding the stable σR. The amount of WblC protein and its binding to the sigRp1 promoter in vivo increased upon antibiotic treatment. A similar phenomenon appears to exist in Mycobacterium tuberculosis as well. These findings reveal a novel antibiotic-induced resistance mechanism conserved among actinomycetes, and also give an explicit example of overlap in cellular damage and defense mechanisms between thiol-oxidative and anti- translational stresses. PMID:27346454

Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota.

PubMed

Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy; Wang, Hua H

2013-08-01

This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection.

Antibiotic stewardship and empirical antibiotic treatment: How can they get along?

PubMed

Zuccaro, Valentina; Columpsi, Paola; Sacchi, Paolo; Lucà, Maria Grazia; Fagiuoli, Stefano; Bruno, Raffaele

2017-06-01

The aim of this review is to focus on the recent knowledge on antibiotic stewardship and empiric antibiotic treatment in cirrhotic patients. The application of antimicrobial stewardship (AMS) rules appears to be the most appropriate strategy to globally manage cirrhotic patients with infectious complications: indeed they represent a unique way to provide both early diagnosis and appropriate therapy in order to avoid not only antibiotic over-prescription but, more importantly, selection and spread of antimicrobial resistance. Moreover, cirrhotic patients must be considered "frail" and susceptible to healthcare associated infections: applying AMS policies would assure a cost reduction and thus contribute to the improvement of public health strategies. Copyright © 2017. Published by Elsevier Ltd.

A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance

PubMed Central

2014-01-01

Background Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substantially less than from hospitalized patients on whom guidelines are often based. We therefore chose to assess the relationship between the antibiotic resistance pattern of bacteria circulating in the community and the consumption of antibiotics in the community. Methods Both gray literature and published scientific literature in English and other European languages was examined. Multiple regression analysis was used to analyse whether studies found a positive relationship between antibiotic consumption and resistance. A subsequent meta-analysis and meta-regression was conducted for studies for which a common effect size measure (odds ratio) could be calculated. Results Electronic searches identified 974 studies but only 243 studies were considered eligible for inclusion by the two independent reviewers who extracted the data. A binomial test revealed a positive relationship between antibiotic consumption and resistance (p < .001) but multiple regression modelling did not produce any significant predictors of study outcome. The meta-analysis generated a significant pooled odds ratio of 2.3 (95% confidence interval 2.2 to 2.5) with a meta-regression producing several significant predictors (F(10,77) = 5.82, p < .01). Countries in southern Europe produced a stronger link between consumption and resistance than other regions. Conclusions Using a large set of studies we found that antibiotic consumption is associated with the development of antibiotic resistance. A subsequent meta-analysis, with a subsample of the studies, generated several significant predictors. Countries in southern Europe produced a stronger link between consumption and resistance than other

What Can Be Done about Antibiotic Resistance?

MedlinePlus

... antibiotics for treating human disease. (See Antibiotics in agriculture .) Is there any international action on the antibiotic ... and reducing antibiotic use in animal farming and agriculture. Experts agree that a global system for tracking ...

Efficient removal of antibiotics in surface-flow constructed wetlands, with no observed impact on antibiotic resistance genes.

PubMed

Berglund, Björn; Khan, Ghazanfar Ali; Weisner, Stefan E B; Ehde, Per Magnus; Fick, Jerker; Lindgren, Per-Eric

2014-04-01

Recently, there have been growing concerns about pharmaceuticals including antibiotics as environmental contaminants. Antibiotics of concentrations commonly encountered in wastewater have been suggested to affect bacterial population dynamics and to promote dissemination of antibiotic resistance. Conventional wastewater treatment processes do not always adequately remove pharmaceuticals causing environmental dissemination of low levels of these compounds. Using constructed wetlands as an additional treatment step after sewage treatment plants have been proposed as a cheap alternative to increase reduction of wastewater contaminants, however this means that the natural microbial community of the wetlands becomes exposed to elevated levels of antibiotics. In this study, experimental surface-flow wetlands in Sweden were continuously exposed to antibiotics of concentrations commonly encountered in wastewater. The aim was to assess the antibiotic removal efficiency of constructed wetlands and to evaluate the impact of low levels of antibiotics on bacterial diversity, resistance development and expression in the wetland bacterial community. Antibiotic concentrations were measured using liquid chromatography-mass spectrometry and the effect on the bacterial diversity was assessed with 16S rRNA-based denaturing gradient gel electrophoresis. Real-time PCR was used to detect and quantify antibiotic resistance genes and integrons in the wetlands, during and after the exposure period. The results indicated that the antibiotic removal efficiency of constructed wetlands was comparable to conventional wastewater treatment schemes. Furthermore, short-term treatment of the constructed wetlands with environmentally relevant concentrations (i.e. 100-2000 ng×l(-1)) of antibiotics did not significantly affect resistance gene concentrations, suggesting that surface-flow constructed wetlands are well-suited for wastewater treatment purposes. Copyright © 2014 Elsevier B.V. All rights

Fate and transport of veterinary antibiotics, antibiotic-resistant bacteria, and antibiotic resistance gene from fields receiving poultry manure during storm events

USDA-ARS?s Scientific Manuscript database

Antimicrobials are used in production agriculture to treat disease and promote animal growth, but the presence of antibiotics in the environment raises concern about widespread antibiotic resistance. This study documents the occurrence and transport of tylosin, tetracycline, enterococci resistant to...

Excretion of Antibiotic Resistance Genes by Dairy Calves Fed Milk Replacers with Varying Doses of Antibiotics

PubMed Central

Thames, Callie H.; Pruden, Amy; James, Robert E.; Ray, Partha P.; Knowlton, Katharine F.

2012-01-01

Elevated levels of antibiotic resistance genes (ARGs) in soil and water have been linked to livestock farms and in some cases feed antibiotics may select for antibiotic resistant gut microbiota. The purpose of this study was to examine the establishment of ARGs in the feces of calves receiving milk replacer containing no antibiotics versus subtherapeutic or therapeutic doses of tetracycline and neomycin. The effect of antibiotics on calf health was also of interest. Twenty-eight male and female dairy calves were assigned to one of the three antibiotic treatment groups at birth and fecal samples were collected at weeks 6, 7 (prior to weaning), and 12 (5 weeks after weaning). ARGs corresponding to the tetracycline (tetC, tetG, tetO, tetW, and tetX), macrolide (ermB, ermF), and sulfonamide (sul1, sul2) classes of antibiotics along with the class I integron gene, intI1, were monitored by quantitative polymerase chain reaction as potential indicators of direct selection, co-selection, or horizontal gene transfer of ARGs. Surprisingly, there was no significant effect of antibiotic treatment on the absolute abundance (gene copies per gram wet manure) of any of the ARGs except ermF, which was lower in the antibiotic-treated calf manure, presumably because a significant portion of host bacterial cells carrying ermF were not resistant to tetracycline or neomycin. However, relative abundance (gene copies normalized to 16S rRNA genes) of tetO was higher in calves fed the highest dose of antibiotic than in the other treatments. All genes, except tetC and intI1, were detectable in feces from 6 weeks onward, and tetW and tetG significantly increased (P < 0.10), even in control calves. Overall, the results provide new insight into the colonization of calf gut flora with ARGs in the early weeks. Although feed antibiotics exerted little effect on the ARGs monitored in this study, the fact that they also provided no health benefit suggests that the greater than conventional

Antibiotic losses from unprotected manure stockpiles.

PubMed

Dolliver, Holly A S; Gupta, Satish C

2008-01-01

Manure management is a major concern in livestock production systems. Although historically the primary concerns have been nutrients and pathogens, manure is also a source of emerging contaminants, such as antibiotics, to the environment. There is a growing concern that antibiotics in manure are reaching surface and ground waters and contributing to the development and spread of antibiotic resistance in the environment. One such pathway is through leaching and runoff from manure stockpiles. In this study, we quantified chlortetracycline, monensin, and tylosin losses in runoff from beef manure stockpiles during two separate but consecutive experiments representing different weather conditions (i.e., temperature and precipitation amount and form). Concentrations of chlortetracycline, monensin, and tylosin in runoff were positively correlated with initial concentrations of antibiotics in manure. The highest concentrations of chlortetracycline, monensin, and tylosin in runoff were 210, 3175, and 2544 microg L(-1), respectively. Relative antibiotic losses were primarily a function of water losses. In the experiment that had higher runoff water losses, antibiotic losses ranged from 1.2 to 1.8% of total extractable antibiotics in manure. In the experiment with lower runoff water losses, antibiotic losses varied from 0.2 to 0.6% of the total extractable antibiotics in manure. Manure analysis over time suggests that in situ degradation is an important mechanism for antibiotic losses. Degradation losses during manure stockpiling may exceed cumulative losses from runoff events. Storing manure in protected (i.e., covered) facilities could reduce the risk of aquatic contamination associated with manure stockpiling and other outdoor manure management practices.

Antibiotics-First Versus Surgery for Appendicitis: A US Pilot Randomized Controlled Trial Allowing Outpatient Antibiotic Management.

PubMed

Talan, David A; Saltzman, Darin J; Mower, William R; Krishnadasan, Anusha; Jude, Cecilia M; Amii, Ricky; DeUgarte, Daniel A; Wu, James X; Pathmarajah, Kavitha; Morim, Ashkan; Moran, Gregory J

2017-07-01

Randomized trials suggest that nonoperative treatment of uncomplicated appendicitis with antibiotics-first is safe. No trial has evaluated outpatient treatment and no US randomized trial has been conducted, to our knowledge. This pilot study assessed feasibility of a multicenter US study comparing antibiotics-first, including outpatient management, with appendectomy. Patients aged 5 years or older with uncomplicated appendicitis at 1 US hospital were randomized to appendectomy or intravenous ertapenem greater than or equal to 48 hours and oral cefdinir and metronidazole. Stable antibiotics-first-treated participants older than 13 years could be discharged after greater than or equal to 6-hour emergency department (ED) observation with next-day follow-up. Outcomes included 1-month major complication rate (primary) and hospital duration, pain, disability, quality of life, and hospital charges, and antibiotics-first appendectomy rate. Of 48 eligible patients, 30 (62.5%) consented, of whom 16 (53.3%) were randomized to antibiotics-first and 14 (46.7%) to appendectomy. Median age was 33 years (range 9 to 73 years), median WBC count was 15,000/μL (range 6,200 to 23,100/μL), and median computed tomography appendiceal diameter was 10 mm (range 7 to 18 mm). Of 15 antibiotic-treated adults, 14 (93.3%) were discharged from the ED and all had symptom resolution. At 1 month, major complications occurred in 2 appendectomy participants (14.3%; 95% confidence interval [CI] 1.8% to 42.8%) and 1 antibiotics-first participant (6.3%; 95% CI 0.2% to 30.2%). Antibiotics-first participants had less total hospital time than appendectomy participants, 16.2 versus 42.1 hours, respectively. Antibiotics-first-treated participants had less pain and disability. During median 12-month follow-up, 2 of 15 antibiotics-first-treated participants (13.3%; 95% CI 3.7% to 37.9%) developed appendicitis and 1 was treated successfully with antibiotics; 1 had appendectomy. No more major complications

Antibiotic Use in Small Community Hospitals.

PubMed

Stenehjem, Edward; Hersh, Adam L; Sheng, Xiaoming; Jones, Peter; Buckel, Whitney R; Lloyd, James F; Howe, Stephen; Evans, R Scott; Greene, Tom; Pavia, Andrew T

2016-11-15

 Antibiotic use and misuse is driving drug resistance. Much of US healthcare takes place in small community hospitals (SCHs); 70% of all US hospitals have <200 beds. Antibiotic use in SCHs is poorly described. We evaluated antibiotic use using data from the National Healthcare and Safety Network antimicrobial use option from the Centers for Disease Control and Prevention.  We used Intermountain Healthcare's monthly antibiotic use reports for 19 hospitals from 2011 to 2013. Hospital care units were categorized as intensive care, medical/surgical, pediatric, or miscellaneous. Antibiotics were categorized based on spectrum of coverage. Antibiotic use rates, expressed as days of therapy per 1000 patient-days (DOT/1000PD), were calculated for each SCH and compared with rates in large community hospitals (LCHs). Negative-binomial regression was used to relate antibiotic use to predictor variables.  Total antibiotic use rates varied widely across the 15 SCHs (median, 436 DOT/1000PD; range, 134-671 DOT/1000PD) and were similar to rates in 4 LCHs (509 DOT/1000PD; 406-597 DOT/1000PD). The proportion of patient-days spent in the respective unit types varied substantially within SCHs and had a large impact on facility-level rates. Broad-spectrum antibiotics accounted for 26% of use in SCHs (range, 8%-36%), similar to the proportion in LCHs (32%; range, 26%-37%). Case mix index, proportion of patient-days in specific unit types, and season were significant predictors of antibiotic use.  There is substantial variation in patterns of antibiotic use among SCHs. Overall usage in SCHs is similar to usage in LCHs. Small hospitals need to become a focus of stewardship efforts. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Continuous versus intermittent antibiotics for bronchiectasis.

PubMed

Donovan, Tim; Felix, Lambert M; Chalmers, James D; Milan, Stephen J; Mathioudakis, Alexander G; Spencer, Sally

2018-06-03

Bronchiectasis is a chronic airway disease characterised by a destructive cycle of recurrent airway infection, inflammation and tissue damage. Antibiotics are a main treatment for bronchiectasis. The aim of continuous therapy with prophylactic antibiotics is to suppress bacterial load, but bacteria may become resistant to the antibiotic, leading to a loss of effectiveness. On the other hand, intermittent prophylactic antibiotics, given over a predefined duration and interval, may reduce antibiotic selection pressure and reduce or prevent the development of resistance. This systematic review aimed to evaluate the current evidence for studies comparing continuous versus intermittent administration of antibiotic treatment in bronchiectasis in terms of clinical efficacy, the emergence of resistance and serious adverse events. To evaluate the effectiveness of continuous versus intermittent antibiotics in the treatment of adults and children with bronchiectasis, using the primary outcomes of exacerbations, antibiotic resistance and serious adverse events. On 1 August 2017 and 4 May 2018 we searched the Cochrane Airways Review Group Specialised Register (CAGR), CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. On 25 September 2017 and 4 May 2018 we also searched www.clinicaltrials.gov, the World Health Organization (WHO) trials portal, conference proceedings and the reference lists of existing systematic reviews. We planned to include randomised controlled trials (RCTs) of adults or children with bronchiectasis that compared continuous versus intermittent administration of long-term prophylactic antibiotics of at least three months' duration. We considered eligible studies reported as full-text articles, as abstracts only and unpublished data. Two review authors independently screened the search results and full-text reports. We identified 268 unique records. Of these we retrieved and examined 126 full-text reports, representing 114 studies, but none of these studies

Sublethal Concentrations of Antibiotics Cause Shift to Anaerobic Metabolism in Listeria monocytogenes and Induce Phenotypes Linked to Antibiotic Tolerance

PubMed Central

Knudsen, Gitte M.; Fromberg, Arvid; Ng, Yin; Gram, Lone

2016-01-01

The human pathogenic bacterium Listeria monocytogenes is exposed to antibiotics both during clinical treatment and in its saprophytic lifestyle. As one of the keys to successful treatment is continued antibiotic sensitivity, the purpose of this study was to determine if exposure to sublethal antibiotic concentrations would affect the bacterial physiology and induce antibiotic tolerance. Transcriptomic analyses demonstrated that each of the four antibiotics tested caused an antibiotic-specific gene expression pattern related to mode-of-action of the particular antibiotic. All four antibiotics caused the same changes in expression of several metabolic genes indicating a shift from aerobic to anaerobic metabolism and higher ethanol production. A mutant in the bifunctional acetaldehyde-CoA/alcohol dehydrogenase encoded by lmo1634 did not have altered antibiotic tolerance. However, a mutant in lmo1179 (eutE) encoding an aldehyde oxidoreductase where rerouting caused increased ethanol production was tolerant to three of four antibiotics tested. This shift in metabolism could be a survival strategy in response to antibiotics to avoid generation of ROS production from respiration by oxidation of NADH through ethanol production. The monocin locus encoding a cryptic prophage was induced by co-trimoxazole and repressed by ampicillin and gentamicin, and this correlated with an observed antibiotic-dependent biofilm formation. A monocin mutant (ΔlmaDCBA) had increased biofilm formation when exposed to increasing concentration of co-trimoxazole similar to the wild type, but was more tolerant to killing by co-trimoxazole and ampicillin. Thus, sublethal concentrations of antibiotics caused metabolic and physiological changes indicating that the organism is preparing to withstand lethal antibiotic concentrations. PMID:27462313

Timeliness and use of antibiotic prophylaxis in selected inpatient surgical procedures. The Antibiotic Prophylaxis Study Group.

PubMed

Silver, A; Eichorn, A; Kral, J; Pickett, G; Barie, P; Pryor, V; Dearie, M B

1996-06-01

Twenty-five percent of all nosocomial infections are wound infections. Professional guidelines support the timely use of preoperative prophylaxis for prevention of postoperative wound infections. Barriers exist in implementing this practice. IPRO, the New York State peer review organization, as part of the Health Care Financing Administration's Health Care Quality Improvement Program, sought to determine the proportion of patients receiving timely antibiotic prophylaxis for aortic grafts, hip replacements and colon resections in 44 hospitals in New York State. IPRO conducted a retrospective medical record review of 44 hospitals through out New York State stratified for teaching, nonteaching status. A sample was drawn of 2651 patients, 2256 from Medicare and 395 from Medicaid, undergoing either abdominal aortic aneurysm repair, partial or total hip replacement or large bowel resection. The study determined the proportion of patients who had documentation of receiving antibiotics and those who received antibiotics timely, that is less than or equal to 2 hours preoperatively. Eighty-six percent of patients had documentation of receiving an antibiotic. Forty-six percent of aneurysm repairs and 60% of hip replacements had evidence of receiving timely antibiotic prophylaxis, that is within 2 hours prior to surgery. For colon resections, 73% of cases had either oral prophylaxis or timely parenteral therapy. An increased proportion of patients had received parenteral antibiotics prematurely as the surgical start time occurred later in the day. A total of 44 different antibiotics were recorded for prophylaxis. Antibiotic prophylaxis was performed in 81% to 94% of cases, however, anywhere from 27% to 54% of all cases did not receive antibiotics in a timely fashion. By delegating implementation of ordered antibiotic prophylaxis to the anesthesia team, timing may be improved and the incidence of postoperative wound infections may decrease.

Trends in antibiotic utilization in Vancouver associated with a community education program on antibiotic use.

PubMed

Fuertes, Elaine Isabelle; Henry, Bonnie; Marra, Fawziah; Wong, Hubert; Patrick, David M

2010-01-01

"Do Bugs Need Drugs" (DBND) is a community education program that was implemented in British Columbia (BC) in September 2005 to decrease inappropriate antibiotic use. This study conducted descriptive analyses of the association between DBND and changes in overall, pediatric, drug-specific, and indication-specific antibiotic utilization rates in Vancouver, BC. Utilization data on all oral solid and liquid antibiotics classified as "antibacterials for systemic use" were obtained from BC PharmaNet for the years 1996 to 2008. Utilization data were linked to physician billing data to allow indication-specific analyses. Following conversion to the defined daily dose (DDD), the Holt-Winters exponential smoothing method was used to project expected antibiotic use in the period after implementation based on use prior to implementation. Differences between expected and observed utilization rates were calculated. Overall antibiotic use has stabilized in recent years (16.2 DDD/1000 population/day in 2008). Fluoroquinolone use remains high (1.5 DDD/1000 population/day), as does the steadily increasing use of newer macrolides (1.1 to 2.7 DDD/1000 population/day between 1996 and 2008). Encouraging declines in overall and indication-specific prescription rates among children were observed. Following 3 years of DBND activities, antibiotic use was 5.8% lower than expected and the number of prescriptions dispensed to children was 10.6% lower than expected. This ecological study reports improvements in antibiotic use that occurred simultaneously to the delivery of the DBND program in Vancouver. However, we did not find a lowering of all targeted classes. Policy directives limiting the use of certain antibiotics may be required.

Non-antibiotic treatments for bacterial diseases in an era of progressive antibiotic resistance.

PubMed

Opal, Steven M

2016-12-16

The emergence of multi-drug resistant (MDR) microbial pathogens threatens the very foundation upon which standard antibacterial chemotherapy is based. We must consider non-antibiotic solutions to manage invasive bacterial infections. Transition from antibiotics to non-traditional treatments poses real clinical challenges that will not be easy to solve. Antibiotics will continue to reliably treat some infections (e.g., group A streptococci and Treponema pallidum) but will likely need adjuvant therapies or will need to be replaced for many bacterial infections in the future.

Antibiotic therapy for Shigella dysentery.

PubMed

Prince Christopher R H; David, Kirubah V; John, Sushil M; Sankarapandian, Venkatesan

2010-01-20

Shigella dysentery is a relatively common illness and occasionally causes death, worldwide. Mild symptoms are self-limiting but in more severe cases, antibiotics are recommended for cure and preventing relapse. The antibiotics recommended are diverse, have regional differences in sensitivity, and have side effects. To evaluate the efficacy and safety of antibiotics for treating Shigella dysentery. In June 2009 we identified all relevant trials from the following databases: Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, issue 4), MEDLINE, EMBASE, LILACS and the metaRegister of Controlled Trials (mRCT). We also checked conference proceedings for relevant abstracts, and contacted researchers, organizations, and pharmaceutical companies. Randomized controlled trials of antibiotics for Shigella dysentery. Four authors, working in pairs, independently assessed trial eligibility, methodological quality, and extracted data. We calculated risk ratios (RR) with 95% confidence intervals (CI) for dichotomous data, and used the random-effects model for significant heterogeneity. We explored possible sources of heterogeneity, when present, in subgroup analyses of participant age and percentage of participants with confirmed Shigella infection. Sixteen trials (1748 participants), spanning four decades and with differing sensitivity to Shigella isolates, met the inclusion criteria. Seven were judged to be at risk of bias due to inadequate allocation concealment or blinding, and 12 due to incomplete reporting of outcome data. Limited data from one three-armed trial of people with moderately severe illness suggest that antibiotics reduce the episodes of diarrhoea at follow-up (furazolidone versus no drug RR 0.21, 95% CI 0.09 to 0.48, 73 participants; cotrimoxazole versus no drug RR 0.30, 95% CI 0.15 to 0.59, 76 participants).There was insufficient evidence to consider any class of

Antibiotic therapy for Shigella dysentery.

PubMed

Christopher, Prince Rh; David, Kirubah V; John, Sushil M; Sankarapandian, Venkatesan

2010-08-04

Shigella dysentery is a relatively common illness and occasionally causes death, worldwide. Mild symptoms are self-limiting but in more severe cases, antibiotics are recommended for cure and preventing relapse. The antibiotics recommended are diverse, have regional differences in sensitivity, and have side effects. To evaluate the efficacy and safety of antibiotics for treating Shigella dysentery. In June 2009 we identified all relevant trials from the following databases: Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, issue 4), MEDLINE, EMBASE, LILACS and the metaRegister of Controlled Trials (mRCT). We also checked conference proceedings for relevant abstracts, and contacted researchers, organizations, and pharmaceutical companies. Randomized controlled trials of antibiotics for Shigella dysentery. Four authors, working in pairs, independently assessed trial eligibility, methodological quality, and extracted data. We calculated risk ratios (RR) with 95% confidence intervals (CI) for dichotomous data, and used the random-effects model for significant heterogeneity. We explored possible sources of heterogeneity, when present, in subgroup analyses of participant age and percentage of participants with confirmed Shigella infection. Sixteen trials (1748 participants), spanning four decades and with differing sensitivity to Shigella isolates, met the inclusion criteria. Seven were judged to be at risk of bias due to inadequate allocation concealment or blinding, and 12 due to incomplete reporting of outcome data. Limited data from one three-armed trial of people with moderately severe illness suggest that antibiotics reduce the episodes of diarrhoea at follow-up (furazolidone versus no drug RR 0.21, 95% CI 0.09 to 0.48, 73 participants; cotrimoxazole versus no drug RR 0.30, 95% CI 0.15 to 0.59, 76 participants).There was insufficient evidence to consider any class of

Danger of Antibiotic Overuse (For Parents)

MedlinePlus

... against them. This is called bacterial resistance or antibiotic resistance. Treating these resistant bacteria requires higher doses of ... to even the most powerful antibiotics available today. Antibiotic resistance is a widespread problem, and one that the ...

Antibiotic Administration Routes Significantly Influence the Levels of Antibiotic Resistance in Gut Microbiota

PubMed Central

Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy

2013-01-01

This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection. PMID:23689712

A call for antibiotic alternatives research

USDA-ARS?s Scientific Manuscript database

The persistence and spread of antibiotic resistance and decreased profitability of new antibiotics have created the dangerous prospect of ineffective therapies against bacterial diseases. The discovery, development, and application of effective antibiotic alternatives, especially in agriculture, sho...

Validating hospital antibiotic purchasing data as a metric of inpatient antibiotic use

PubMed Central

Tan, Charlie; Ritchie, Michael; Alldred, Jason; Daneman, Nick

2016-01-01

Objectives Antibiotic purchasing data are a widely used, but unsubstantiated, measure of antibiotic consumption. To validate this source, we compared purchasing data from hospitals and external medical databases with patient-level dispensing data. Methods Antibiotic purchasing and dispensing data from internal hospital records and purchasing data from IMS Health were obtained for two hospitals between May 2013 and April 2015. Internal purchasing data were validated against dispensing data, and IMS data were compared with both internal metrics. Scatterplots of individual antimicrobial data points were generated; Pearson's correlation and linear regression coefficients were computed. A secondary analysis re-examined these correlations over shorter calendar periods. Results Internal purchasing data were strongly correlated with dispensing data, with correlation coefficients of 0.90 (95% CI = 0.83–0.95) and 0.98 (95% CI = 0.95–0.99) at hospitals A and B, respectively. Although dispensing data were consistently lower than purchasing data, this was attributed to a single antibiotic at both hospitals. IMS data were favourably correlated with, but underestimated, internal purchasing and dispensing data. This difference was accounted for by eight antibiotics for which direct sales from some manufacturers were not included in the IMS database. The correlation between purchasing and dispensing data was consistent across periods as short as 3 months, but not at monthly intervals. Conclusions Both internal and external antibiotic purchasing data are strongly correlated with dispensing data. If outliers are accounted for appropriately, internal purchasing data could be used for cost-effective evaluation of antimicrobial stewardship programmes, and external data sets could be used for surveillance and research across geographical regions. PMID:26546668

Antibiotic prescribing in dental practice in Belgium.

PubMed

Mainjot, A; D'Hoore, W; Vanheusden, A; Van Nieuwenhuysen, J-P

2009-12-01

To assess the types and frequency of antibiotic prescriptions by Belgian dentists, the indications for antibiotic prescription, and dentists' knowledge about recommended practice in antibiotic use. In this cross-sectional survey, dental practitioners were asked to record information about all antibiotics prescribed to their patients during a 2-week period. The dental practitioners were also asked to complete a self-administered questionnaire regarding demographic data, prescribing practices, and knowledge about antibiotic use. A random sample of 268 Belgian dentists participated in the survey. During the 2-week period, 24 421 patient encounters were recorded; 1033 patients were prescribed an antibiotic (4.2%). The median number of prescriptions per dentist for the 2 weeks was 3. Broad spectrum antibiotics were most commonly prescribed: 82% of all prescriptions were for amoxycillin, amoxycillin-clavulanic acid and clindamycin. Antibiotics were often prescribed in the absence of fever (92.2%) and without any local treatment (54.2%). The most frequent diagnosis for which antibiotics were prescribed was periapical abscess (51.9%). Antibiotics were prescribed to 63.3% of patients with periapical abscess and 4.3% of patients with pulpitis. Patterns of prescriptions were confirmed by the data from the self-reported practice. Discrepancies between observed and recommended practice support the need for educational initiatives to promote rational use of antibiotics in dentistry in Belgium.

Antibiotic pharmacoeconomics: an attempt to find the real cost of hospital antibiotic prescribing.

PubMed Central

Kerr, J. R.; Barr, J. G.; Smyth, E. T.; O'Hare, J.; Bell, P. M.; Callender, M. E.

1993-01-01

Antibiotics account for a large part of all hospital pharmacy budgets, but the actual cost of their prescription is unknown. These costs include intravenous administration, labour, serum antibiotic assay, monitoring of haematological and biochemical indices, disposal of sharps and adverse effects. An in-house method of costing antibiotic therapy is presented, to quantify these hidden expenses. Since not only an awareness, but an accurate quantification, of hidden costs is required, a study of various hospital procedures relating directly to antibiotic therapy was undertaken in an acute medical ward; this involved the identification of particular staff members performing various procedures, consumables used and time taken. The cost of five-day courses of gentamicin, penicillin G, ampicillin, flucloxacillin, cefuroxime, ceftotaxime and erythromycin has been calculated; drug and hidden costs for each are presented graphically for comparison. The breakdown cost for gentamicin is presented to illustrate the method. The costing of adverse effects has not been attempted. We suggest that costings of this sort are used in cost-benefit analysis of antibiotic use. These calculations have been incorporated into a computer spreadsheet and this costing service will be offered to clinical areas of our hospital. PMID:8516976

Exploring the links between antibiotic occurrence, antibiotic resistance, and bacterial communities in water supply reservoirs.

PubMed

Huerta, Belinda; Marti, Elisabet; Gros, Meritxell; López, Pilar; Pompêo, Marcelo; Armengol, Joan; Barceló, Damià; Balcázar, Jose Luis; Rodríguez-Mozaz, Sara; Marcé, Rafael

2013-07-01

Antibiotic resistance represents a growing global health concern due to the overuse and misuse of antibiotics. There is, however, little information about how the selective pressure of clinical antibiotic usage can affect environmental communities in aquatic ecosystems and which bacterial groups might be responsible for dissemination of antibiotic resistance genes (ARGs) into the environment. In this study, chemical and biological characterization of water and sediments from three water supply reservoirs subjected to a wide pollution gradient allowed to draw an accurate picture of the concentration of antibiotics and prevalence of ARGs, in order to evaluate the potential role of ARGs in shaping bacterial communities, and to identify the bacterial groups most probably carrying and disseminating ARGs. Results showed significant correlation between the presence of ARG conferring resistance to macrolides and the composition of bacterial communities, suggesting that antibiotic pollution and the spreading of ARG might play a role in the conformation of bacterial communities in reservoirs. Results also pointed out the bacterial groups Actinobacteria and Firmicutes as the ones probably carrying and disseminating ARGs. The potential effect of antibiotic pollution and the presence of ARGs on the composition of bacterial communities in lacustrine ecosystems prompt the fundamental question about potential effects on bacterial-related ecosystem services supplied by lakes and reservoirs. Copyright © 2013 Elsevier B.V. All rights reserved.

Antibiotic Resistance and Antibiotic Resistance Genes in Escherichia coli Isolates from Hospital Wastewater in Vietnam

PubMed Central

Lan, Pham Thi; Chuc, Nguyen Thi Kim; Hoa, Nguyen Quynh; Nhung, Pham Hong; Thoa, Nguyen Thi Minh; Diwan, Vishal; Tamhankar, Ashok J.; Stålsby Lundborg, Cecilia

2017-01-01

The environmental spread of antibiotic-resistant bacteria has been recognised as a growing public health threat for which hospitals play a significant role. The aims of this study were to investigate the prevalence of antibiotic resistance and antibiotic resistance genes (ARGs) in Escherichia coli isolates from hospital wastewater in Vietnam. Wastewater samples before and after treatment were collected using continuous sampling every month over a year. Standard disk diffusion and E-test were used for antibiotic susceptibility testing. Extended-spectrum beta-lactamase (ESBL) production was tested using combined disk diffusion. ARGs were detected by polymerase chain reactions. Resistance to at least one antibiotic was detected in 83% of isolates; multidrug resistance was found in 32%. The highest resistance prevalence was found for co-trimoxazole (70%) and the lowest for imipenem (1%). Forty-three percent of isolates were ESBL-producing, with the blaTEM gene being more common than blaCTX-M. Co-harbouring of the blaCTX-M, blaTEM and qepA genes was found in 46% of isolates resistant to ciprofloxacin. The large presence of antibiotic-resistant E. coli isolates combined with ARGs in hospital wastewater, even post-treatment, poses a threat to public health. It highlights the need to develop effective processes for hospital wastewater treatment plants to eliminate antibiotic resistant bacteria and ARGs. PMID:28661465

Antibiotic Resistance and Antibiotic Resistance Genes in Escherichia coli Isolates from Hospital Wastewater in Vietnam.

PubMed

Lien, La Thi Quynh; Lan, Pham Thi; Chuc, Nguyen Thi Kim; Hoa, Nguyen Quynh; Nhung, Pham Hong; Thoa, Nguyen Thi Minh; Diwan, Vishal; Tamhankar, Ashok J; Stålsby Lundborg, Cecilia

2017-06-29

The environmental spread of antibiotic-resistant bacteria has been recognised as a growing public health threat for which hospitals play a significant role. The aims of this study were to investigate the prevalence of antibiotic resistance and antibiotic resistance genes (ARGs) in Escherichia coli isolates from hospital wastewater in Vietnam. Wastewater samples before and after treatment were collected using continuous sampling every month over a year. Standard disk diffusion and E-test were used for antibiotic susceptibility testing. Extended-spectrum beta-lactamase (ESBL) production was tested using combined disk diffusion. ARGs were detected by polymerase chain reactions. Resistance to at least one antibiotic was detected in 83% of isolates; multidrug resistance was found in 32%. The highest resistance prevalence was found for co-trimoxazole (70%) and the lowest for imipenem (1%). Forty-three percent of isolates were ESBL-producing, with the bla TEM gene being more common than bla CTX-M . Co-harbouring of the bla CTX-M , bla TEM and qepA genes was found in 46% of isolates resistant to ciprofloxacin. The large presence of antibiotic-resistant E. coli isolates combined with ARGs in hospital wastewater, even post-treatment, poses a threat to public health. It highlights the need to develop effective processes for hospital wastewater treatment plants to eliminate antibiotic resistant bacteria and ARGs.

Think twice: A cognitive perspective of an antibiotic timeout intervention to improve antibiotic use.

PubMed

Jones, Makoto; Butler, Jorie; Graber, Christopher J; Glassman, Peter; Samore, Matthew H; Pollack, Lori A; Weir, Charlene; Goetz, Matthew Bidwell

2017-07-01

To understand clinicians' impressions of and decision-making processes regarding an informatics-supported antibiotic timeout program to re-evaluate the appropriateness of continuing vancomycin and piperacillin/tazobactam. We implemented a multi-pronged informatics intervention, based on Dual Process Theory, to prompt discontinuation of unwarranted vancomycin and piperacillin/tazobactam on or after day three in a large Veterans Affairs Medical Center. Two workflow changes were introduced to facilitate cognitive deliberation about continuing antibiotics at day three: (1) teams completed an electronic template note, and (2) a paper summary of clinical and antibiotic-related information was provided to clinical teams. Shortly after starting the intervention, six focus groups were conducted with users or potential users. Interviews were recorded and transcribed. Iterative thematic analysis identified recurrent themes from feedback. Themes that emerged are represented by the following quotations: (1) captures and controls attention ("it reminds us to think about it"), (2) enhances informed and deliberative reasoning ("it makes you think twice"), (3) redirects decision direction ("…because [there was no indication] I just [discontinued] it without even trying"), (4) fosters autonomy and improves team empowerment ("the template… forces the team to really discuss it"), and (5) limits use of emotion-based heuristics ("my clinical concern is high enough I think they need more aggressive therapy…"). Requiring template completion to continue antibiotics nudged clinicians to re-assess the appropriateness of specified antibiotics. Antibiotic timeouts can encourage deliberation on overprescribed antibiotics without substantially curtailing autonomy. An effective nudge should take into account clinician's time, workflow, and thought processes. Published by Elsevier Inc.

Antibiotics: Precious Goods in Changing Times.

PubMed

Sass, Peter

2017-01-01

Antibiotics represent a first line of defense of diverse microorganisms, which produce and use antibiotics to counteract natural enemies or competitors for nutritional resources in their nearby environment. For antimicrobial activity, nature has invented a great variety of mechanisms of antibiotic action that involve the perturbation of essential bacterial structures or biosynthesis pathways of macromolecules such as the bacterial cell wall, DNA, RNA, or proteins, thereby threatening the specific microbial lifestyle and eventually even survival. However, along with highly inventive modes of antibiotic action, nature also developed a comparable set of resistance mechanisms that help the bacteria to circumvent antibiotic action. Microorganisms have evolved specific adaptive responses that allow appropriately reacting to the presence of antimicrobial agents, ensuring survival during antimicrobial stress. In times of rapid development and spread of antibiotic (multi-)resistance, we need to explore new, resistance-breaking strategies to counteract bacterial infections. This chapter intends to give an overview of common antibiotics and their target pathways. It will also discuss recent advances in finding new antibiotics with novel modes of action, illustrating that nature's repertoire of innovative new antimicrobial agents has not been fully exploited yet, and we still might find new drugs that help to evade established antimicrobial resistance strategies.

Antibiotic effectiveness: balancing conservation against innovation.

PubMed

Laxminarayan, Ramanan

2014-09-12

Antibiotic effectiveness is a natural societal resource that is diminished by antibiotic use. As with other such assets, keeping it available requires both conservation and innovation. Conservation encompasses making the best use of current antibiotic effectiveness by reducing demand through vaccination, infection control, diagnostics, public education, incentives for clinicians to prescribe fewer antibiotics, and restrictions on access to newer, last-resort antibiotics. Innovation includes improving the efficacy of current drugs and replenishing effectiveness by developing new drugs. In this paper, I assess the relative benefits and costs of these two approaches to maintaining our ability to treat infections. Copyright © 2014, American Association for the Advancement of Science.

Antibiotics during childhood and inflammatory bowel disease?

PubMed

2014-10-01

Four epidemiological studies, including two large cohort studies in children aged 17 years or under, have studied the link between antibiotic therapy and inflammatory bowel disease. The risk of inflammatory bowel disease appeared to be twice as high in children exposed to an antibiotic as in unexposed children. The risk appeared higher following exposure during the first year of life, with beta-lactam antibiotics, and with repeated antibiotic courses. One postulated mechanism is through destruction of the anaerobic intestinal flora by antibiotics. In practice, these data provide yet another reason to avoid unnecessarily exposing children to antibiotics.

Self-Medication with Antibiotics, Attitude and Knowledge of Antibiotic Resistance among Community Residents and Undergraduate Students in Northwest Nigeria.

PubMed

Ajibola, Olumide; Omisakin, Olusola Akintoye; Eze, Anthonius Anayochukwu; Omoleke, Semeeh Akinwale

2018-04-27

This study set out to evaluate self-medicated antibiotics and knowledge of antibiotic resistance among undergraduate students and community members in northern Nigeria. Antibiotic consumption pattern, source of prescription, illnesses commonly treated, attitude towards antibiotics, and knowledge of antibiotic resistance were explored using a structured questionnaire. Responses were analyzed and summarized using descriptive statistics. Of the 1230 respondents from undergraduate students and community members, prescription of antibiotics by a physician was 33% and 57%, respectively, amongst undergraduate students and community members. We tested the respondents’ knowledge of antibiotic resistance (ABR) and found that undergraduate students displayed less knowledge that self-medication could lead to ABR (32.6% and 42.2% respectively). Self-medication with antibiotics is highly prevalent in Northwest Nigeria, with most medicines being purchased from un-licensed stores without prescription from a physician. We also observed a significant gap in respondents’ knowledge of ABR. There is an urgent need for public health authorities in Nigeria to enforce existing laws on antibiotics sales and enlighten the people on the dangers of ABR.

Fate and transport of antibiotic residues and antibiotic resistance genes following land application of manure waste.

PubMed

Chee-Sanford, Joanne C; Mackie, Roderick I; Koike, Satoshi; Krapac, Ivan G; Lin, Yu-Feng; Yannarell, Anthony C; Maxwell, Scott; Aminov, Rustam I

2009-01-01

Antibiotics are used in animal livestock production for therapeutic treatment of disease and at subtherapeutic levels for growth promotion and improvement of feed efficiency. It is estimated that approximately 75% of antibiotics are not absorbed by animals and are excreted in waste. Antibiotic resistance selection occurs among gastrointestinal bacteria, which are also excreted in manure and stored in waste holding systems. Land application of animal waste is a common disposal method used in the United States and is a means for environmental entry of both antibiotics and genetic resistance determinants. Concerns for bacterial resistance gene selection and dissemination of resistance genes have prompted interest about the concentrations and biological activity of drug residues and break-down metabolites, and their fate and transport. Fecal bacteria can survive for weeks to months in the environment, depending on species and temperature, however, genetic elements can persist regardless of cell viability. Phylogenetic analyses indicate antibiotic resistance genes have evolved, although some genes have been maintained in bacteria before the modern antibiotic era. Quantitative measurements of drug residues and levels of resistance genes are needed, in addition to understanding the environmental mechanisms of genetic selection, gene acquisition, and the spatiotemporal dynamics of these resistance genes and their bacterial hosts. This review article discusses an accumulation of findings that address aspects of the fate, transport, and persistence of antibiotics and antibiotic resistance genes in natural environments, with emphasis on mechanisms pertaining to soil environments following land application of animal waste effluent.

ASP Strategies and Appropriate Antibiotic Use

PubMed Central

Lee, Brian R; Tribble, Alison; Handy, Lori; Gerber, Jeffrey S; Hersh, Adam L; Kronman, Matthew; Terrill, Cindy; Newland, Jason

2017-01-01

Abstract Background The Infectious Diseases Society of America (IDSA) recommends hospitals implement antimicrobial stewardship programs (ASP) in order to decrease inappropriate antibiotic use due to the rise in antibiotic-resistant infections. Data are limited on the extent to which different ASP strategies influence appropriate antibiotic use. Methods We conducted an online survey in 2016 of U.S. Children’s Hospitals to collect hospital-level information on dedicated ASP effort, ASP monitoring activities, use of audit-feedback, formulary restrictions, rapid diagnostics, etc. During the same period the ASP teams at these hospitals completed 3 point prevalence surveys that documented details on all admitted patients 0–17 years receiving any antibiotics, determined what ASP modifications could be made, and if the antibiotic was appropriate. We employed hierarchical, multivariable logit models to examine which ASP-related, hospital-level strategies were associated with appropriate antibiotic use. Results Thirty hospitals participated. A total of 6,921 patients were included, representing 10,068 total antibiotics. Of these orders, 8,554 (85.0%) were categorized as appropriate, though this varied across sites (range: 68-92%). Additionally, 78.2% of antibiotics did not have recommended modifications. Appropriate antibiotic use was significantly higher for hospitals that relied on rapid diagnostics (aOR: 1.6; P < 0.001) or monitored their days of therapy (DOT) rate (aOR: 1.4; P < 0.001), whereas the presence of either audit-feedback (aOR: 1.04; P = 0.75) or formulary restrictions (aOR: 0.83; P = 0.059) were not associated. Having annual education for all prescribers had increased likelihood of antibiotics having no modification recommendations (aOR: 1.45; P = 0.037). Total ASP FTE was not correlated with hospital-level percent appropriate use (corr: −0.05; P = 0.79) or antibiotic modification recommendations (corr: −0.08; P = 0.67). Conclusion Routine

Off-label abuse of antibiotics by bacteria.

PubMed

Viswanathan, V K

2014-01-01

Antibiotics and antibiotic resistance made news on several fronts in the past year. Many public health organizations, including the CDC, used terms such as "crisis", "catastrophic consequences", and "nightmare scenario" to highlight the rapid emergence and spread of antibiotic resistance. A report from the Pew Commission on Industrial Farm Animal Production, on the fifth anniversary of the publication of its landmark 2008 report, noted that state and federal legislative efforts to limit non-therapeutic use of antibiotics in animal production were thwarted by drug and food animal industries. In its lobbying disclosures, the Farm Bureau stated that such efforts to limit use of animal antibiotics were "based on emotion and no credible peer reviewed science." Meanwhile, there have been inexorable advances in our understanding of the molecular mechanisms by which antibiotics induce diversity and resistance in bacteria. This article reviews one study that probed the role of the bacterial general stress response in sub-inhibitory antibiotic-induced mutagenesis and antibiotic resistance.

Prophylactic antibiotics for penetrating abdominal trauma.

PubMed

Brand, Martin; Grieve, Andrew

2013-11-18

Penetrating abdominal trauma occurs when the peritoneal cavity is breached. Routine laparotomy for penetrating abdominal injuries began in the 1800s, with antibiotics first being used in World War II to combat septic complications associated with these injuries. This practice was marked with a reduction in sepsis-related mortality and morbidity. Whether prophylactic antibiotics are required in the prevention of infective complications following penetrating abdominal trauma is controversial, however, as no randomised placebo controlled trials have been published to date. There has also been debate about the timing of antibiotic prophylaxis. In 1972 Fullen noted a 7% to 11% post-surgical infection rate with pre-operative antibiotics, a 33% to 57% infection rate with intra-operative antibiotic administration and 30% to 70% infection rate with only post-operative antibiotic administration. Current guidelines state there is sufficient class I evidence to support the use of a single pre-operative broad spectrum antibiotic dose, with aerobic and anaerobic cover, and continuation (up to 24 hours) only in the event of a hollow viscus perforation found at exploratory laparotomy. To assess the benefits and harms of prophylactic antibiotics administered for penetrating abdominal injuries for the reduction of the incidence of septic complications, such as septicaemia, intra-abdominal abscesses and wound infections. Searches were not restricted by date, language or publication status. We searched the following electronic databases: the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library 2013, issue 12 of 12), MEDLINE (OvidSP), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S) and PubMed. Searches were last conducted in January 2013. All randomised controlled trials of antibiotic prophylaxis in patients with penetrating abdominal trauma versus no

Antibiotic Production by Anaerobic Bacteria1

PubMed Central

Sturgen, Nancy O.; Casida, L. E.

1962-01-01

Soils from aerobic and anaerobic sources were investigated for the possible presence of bacteria which produce antibiotics under anaerobic conditions of growth. The screening techniques devised for this study yielded 157 soil bacteria which, during anaerobic growth, produced antibiotic activity against aerobic test bacteria. Studies on choice of media, presence of oxygen, and changes in antibiotic activity during growth indicated that representative strains of these bacteria produced mixtures of antibiotics. The activity was heat labile. PMID:13918037

[Anti-amebic effect of polyenic antibiotics].

PubMed

Liubimova, L K; Ovnanian, K O; Ivanova, L N

1985-03-01

All-Union Research technological Institute of Antibiotics and Medical Enzymes, Leningrad. Institute of Epidemiology, Virology and medical parasitology, Ministry of Health of the Armenian SSR. The effect of polyenic antibiotics made in the USSR on development of E. histolytica and E. moshkovski was studied. The following antibiotics were used: levorin and its derivatives, mycoheptin, amphotericin B, amphoglucamine and nystatin. The antibiotics were compared with emetine and metronidazole. Some drugs of the imidazole group were also included into the study. On the whole 15 drugs were tested for their antiamebic activity. All the polyenic antibiotics showed a high antiamebic activity. Levorin and its derivatives were the most active. Their MICs ranged from 0.1 to 5.38 micrograms/ml. The most active of the new imidazoles was 100 times less effective than sodium levorin. The studies show that the polyenic antibiotics have an antiamebic activity and a broad antiprotozoal spectrum.

An International Model for Antibiotics Regulation.

PubMed

Aguirre, Emilie

We face a global antibiotics resistance crisis. Antibiotic drugs are rapidly losing their effectiveness, potentially propelling us toward a post-antibiotic world. The largest use of antibiotics in the world is in food-producing animals. Food producers administer these drugs in routine, low doses—the types of doses that are incidentally the most conducive to breeding antibiotic resistance. In general, individual countries have been too slow to act in regulating misuse and overuse of antibiotics in foodproducing animals. This problem will only worsen with the significant projected growth in meat consumption and production expected in emerging economies in the near future. Although individual countries regulating antibiotics can have important effects, one country alone cannot insulate itself entirely from the effects of antibiotic resistance, nor can one country solve the crisis for itself or for the world. The global nature of the food system and the urgency of the problem require immediate global solutions. Adapting a democratic experimentalist approach at the international level can help achieve this goal. Using an international democratic experimentalist framework in conjunction with the World Organization for Animal Health (OIE) would provide for increased systematized data collection and lead to heightened, scientifically informed OIE standards, enforceable by the World Trade Organization (WTO), which could have a significant impact on the reduction of subtherapeutic use of antibiotics internationally. International democratic experimentalism addresses the global intricacy, time sensitivity, context- and culture-specificity, and knowledgeintensiveness of this problem. By encouraging more countries to experiment to solve this problem, the democratic experimentalist model would help develop a larger database of solutions to enable more meaningful cross-country comparisons across a wider range of contexts. This approach maintains democratic governance and

Overview: Global and Local Impact of Antibiotic Resistance.

PubMed

Watkins, Richard R; Bonomo, Robert A

2016-06-01

The rapid and ongoing spread of antibiotic resistance poses a serious threat to global public health. The indiscriminant use of antibiotics in agriculture and human medicine along with increasingly connected societies has fueled the distribution of antibiotic-resistant bacteria. These factors together have led to rising numbers of infections caused by multidrug-resistant and pan-resistant bacteria, with increases in morbidity and mortality. This article summarizes the trends in antibiotic resistance, discusses the impact of antibiotic resistance on society, and reviews the use of antibiotics in agriculture. Feasible ways to tackle antibiotic resistance to avert a post-antibiotic era are suggested. Copyright © 2016 Elsevier Inc. All rights reserved.

Constraining the use of antibiotics: applying Scanlon's contractualism.

PubMed

Millar, Michael

2012-08-01

Decisions to use antibiotics require that patient interests are balanced against the public good, that is, control of antibiotic resistance. Patients carry the risks of suboptimal antibiotic treatment and many physicians are reluctant to impose even small avoidable risks on patients. At the same time, antibiotics are overused and antibiotic-resistant microbes are contributing an increasing burden of adverse patient outcomes. It is the criteria that we can use to reject the use of antibiotics that is the focus of this paper. Scanlon's contractualism explains why antibiotics should not be used to gain small benefits, even when the direct costs of antibiotics are low. We know that some individuals now (and probably more in the future will) carry a burden of irretrievable harm as a consequence of treatment- (antibiotic-) resistant infection. If we accept that the dominant justification for use of antibiotics is to prevent irretrievable harm to an individual or contact, then the use of antibiotics for self-limiting conditions, or for the treatment of individuals with conditions for which antibiotics do not substantially impact on outcomes (eg, in the latter stages of terminal illness), or for access based on preference or willingness to pay (internet or over-the-counter access), or the use of antibiotics as animal growth promoters can be rejected. Scanlon's approach also suggests that, with few new antibiotics in the pipeline and an increasing burden of disease attributable to resistant microbes, control of the spread of antibiotic-resistant microbes should be given increasing priority.

Lessons from the Environmental Antibiotic Resistome.

PubMed

Surette, Matthew D; Wright, Gerard D

2017-09-08

Antibiotic resistance is a global public health issue of growing proportions. All antibiotics are susceptible to resistance. The evidence is now clear that the environment is the single largest source and reservoir of resistance. Soil, aquatic, atmospheric, animal-associated, and built ecosystems are home to microbes that harbor antibiotic resistance elements and the means to mobilize them. The diversity and abundance of resistance in the environment is consistent with the ancient origins of antibiotics and a variety of studies support a long natural history of associated resistance. The implications are clear: Understanding the evolution of resistance in the environment, its diversity, and mechanisms is essential to the management of our existing and future antibiotic resources.

Validating hospital antibiotic purchasing data as a metric of inpatient antibiotic use.

PubMed

Tan, Charlie; Ritchie, Michael; Alldred, Jason; Daneman, Nick

2016-02-01

Antibiotic purchasing data are a widely used, but unsubstantiated, measure of antibiotic consumption. To validate this source, we compared purchasing data from hospitals and external medical databases with patient-level dispensing data. Antibiotic purchasing and dispensing data from internal hospital records and purchasing data from IMS Health were obtained for two hospitals between May 2013 and April 2015. Internal purchasing data were validated against dispensing data, and IMS data were compared with both internal metrics. Scatterplots of individual antimicrobial data points were generated; Pearson's correlation and linear regression coefficients were computed. A secondary analysis re-examined these correlations over shorter calendar periods. Internal purchasing data were strongly correlated with dispensing data, with correlation coefficients of 0.90 (95% CI = 0.83-0.95) and 0.98 (95% CI = 0.95-0.99) at hospitals A and B, respectively. Although dispensing data were consistently lower than purchasing data, this was attributed to a single antibiotic at both hospitals. IMS data were favourably correlated with, but underestimated, internal purchasing and dispensing data. This difference was accounted for by eight antibiotics for which direct sales from some manufacturers were not included in the IMS database. The correlation between purchasing and dispensing data was consistent across periods as short as 3 months, but not at monthly intervals. Both internal and external antibiotic purchasing data are strongly correlated with dispensing data. If outliers are accounted for appropriately, internal purchasing data could be used for cost-effective evaluation of antimicrobial stewardship programmes, and external data sets could be used for surveillance and research across geographical regions. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e

Relationships between antibiotics and antibiotic resistance gene levels in municipal solid waste leachates in Shanghai, China.

PubMed

Wu, Dong; Huang, Zhiting; Yang, Kai; Graham, David; Xie, Bing

2015-04-07

Many studies have quantified antibiotics and antibiotic resistance gene (ARG) levels in soils, surface waters, and waste treatment plants (WTPs). However, similar work on municipal solid waste (MSW) landfill leachates is limited, which is concerning because antibiotics disposal is often in the MSW stream. Here we quantified 20 sulfonamide (SA), quinolone (FQ), tetracycline (TC), macrolide (ML), and chloramphenicol (CP) antibiotics, and six ARGs (sul1, sul2, tetQ, tetM, ermB, and mefA) in MSW leachates from two Shanghai transfer stations (TS; sites Hulin (HL) and Xupu (XP)) and one landfill reservoir (LR) in April and July 2014. Antibiotic levels were higher in TS than LR leachates (985 ± 1965 ng/L vs 345 ± 932 ng/L, n = 40), which was because of very high levels in the HL leachates (averaging at 1676 ± 5175 ng/L, n = 40). The mean MLs (3561 ± 8377 ng/L, n = 12), FQs (975 ± 1608 ng/L, n = 24), and SAs (402 ± 704 ng/L, n = 42) classes of antibiotics were highest across all samples. ARGs were detected in all leachate samples with normalized sul2 and ermB levels being especially elevated (-1.37 ± 1.2 and -1.76 ± 1.6 log (copies/16S-rDNA), respectively). However, ARG abundances did not correlate with detected antibiotic levels, except for tetW and tetQ with TC levels (r = 0.88 and 0.81, respectively). In contrast, most measured ARGs did significantly correlate with heavy metal levels (p < 0.05), especially with Cd and Cr. This study shows high levels of ARGs and antibiotics can prevail in MSW leachates and landfills may be an underappreciated as a source of antibiotics and ARGs to the environment.

Antibiotic Resistance in Plant-Pathogenic Bacteria.

PubMed

Sundin, George W; Wang, Nian

2018-06-01

Antibiotics have been used for the management of relatively few bacterial plant diseases and are largely restricted to high-value fruit crops because of the expense involved. Antibiotic resistance in plant-pathogenic bacteria has become a problem in pathosystems where these antibiotics have been used for many years. Where the genetic basis for resistance has been examined, antibiotic resistance in plant pathogens has most often evolved through the acquisition of a resistance determinant via horizontal gene transfer. For example, the strAB streptomycin-resistance genes occur in Erwinia amylovora, Pseudomonas syringae, and Xanthomonas campestris, and these genes have presumably been acquired from nonpathogenic epiphytic bacteria colocated on plant hosts under antibiotic selection. We currently lack knowledge of the effect of the microbiome of commensal organisms on the potential of plant pathogens to evolve antibiotic resistance. Such knowledge is critical to the development of robust resistance management strategies to ensure the safe and effective continued use of antibiotics in the management of critically important diseases. Expected final online publication date for the Annual Review of Phytopathology Volume 56 is August 25, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Antibiotic stewardship in community-acquired pneumonia.

PubMed

Viasus, Diego; Vecino-Moreno, Milly; De La Hoz, Juan M; Carratalà, Jordi

2017-04-01

Community-acquired pneumonia (CAP) continues to be associated with significant mortality and morbidity. As with other infectious diseases, in recent years there has been a marked increase in resistance to the antibiotics commonly used against the pathogens that cause CAP. Antimicrobial stewardship denotes coordinated interventions to improve and measure the appropriate use of antibiotics by encouraging the selection of optimal drug regimens. Areas covered: Several elements can be applied to antibiotic stewardship strategies for CAP in order to maintain or improve patient outcomes. In this regard, antibiotic de-escalation, duration of antibiotic treatment, adherence to CAP guidelines recommendations about empirical treatment, and switching from intravenous to oral antibiotic therapy may each be relevant in this context. Antimicrobial stewardship strategies, such as prospective audit with intervention and feedback, clinical pathways, and dedicated multidisciplinary teams, that have included some of these elements have demonstrated improvements in antimicrobial use for CAP without negatively affecting clinical outcomes. Expert commentary: Although there are a limited number of randomized clinical studies addressing antimicrobial stewardship strategies in CAP, there is evidence that antibiotic stewardship initiatives can be securely applied, providing benefits to both healthcare systems and patients.

DNA-aptamers binding aminoglycoside antibiotics.

PubMed

Nikolaus, Nadia; Strehlitz, Beate

2014-02-21

Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminoglycoside antibiotic kanamycin A with the aim of constructing a robust and functional assay that can be used for water analysis. With this work we show that aptamers that were derived from a Capture-SELEX procedure targeting against kanamycin A also display binding to related aminoglycoside antibiotics. The binding patterns differ among all tested aptamers so that there are highly substance specific aptamers and more group specific aptamers binding to a different variety of aminoglycoside antibiotics. Also the region of the aminoglycoside antibiotics responsible for aptamer binding can be estimated. Affinities of the different aptamers for their target substance, kanamycin A, are measured with different approaches and are in the micromolar range. Finally, the proof of principle of an assay for detection of kanamycin A in a real water sample is given.

Dual antibiotics for bronchiectasis.

PubMed

Felix, Lambert M; Grundy, Seamus; Milan, Stephen J; Armstrong, Ross; Harrison, Haley; Lynes, Dave; Spencer, Sally

2018-06-11

Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation of the smaller airways and associated with a mortality rate greater than twice that of the general population. Antibiotics serve as front-line therapy for managing bacterial load, but their use is weighed against the development of antibiotic resistance. Dual antibiotic therapy has the potential to suppress infection from multiple strains of bacteria, leading to more successful treatment of exacerbations, reduced symptoms, and improved quality of life. Further evidence is required on the efficacy of dual antibiotics in terms of management of exacerbations and extent of antibiotic resistance. To evaluate the effects of dual antibiotics in the treatment of adults and children with bronchiectasis. We identified studies from the Cochrane Airways Group Specialised Register (CAGR), which includes the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine (AMED), and PsycINFO, as well as studies obtained by handsearching of journals/abstracts. We also searched the following trial registries: US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform. We imposed no restriction on language of publication. We conducted our search in October 2017. We searched for randomised controlled trials comparing dual antibiotics versus a single antibiotic for short-term (< 4 weeks) or long-term management of bronchiectasis diagnosed in adults and/or children by bronchography, plain film chest radiography, or high-resolution computed tomography. Primary outcomes included exacerbations, length of hospitalisation, and serious adverse events. Secondary outcomes were response rates, emergence of resistance to antibiotics, systemic markers of infection, sputum

Macrolide antibiotics for cystic fibrosis.

PubMed

Southern, Kevin W; Barker, Pierre M; Solis-Moya, Arturo; Patel, Latifa

2012-11-14

Macrolide antibiotics may have a modifying role in diseases which involve airway infection and inflammation, like cystic fibrosis. To test the hypotheses that, in people with cystic fibrosis, macrolide antibiotics: 1. improve clinical status compared to placebo or another antibiotic; 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.We contacted investigators known to work in the field, previous authors and pharmaceutical companies manufacturing macrolide antibiotics for unpublished or follow-up data (May 2010).Latest search of the Group's Cystic Fibrosis Trials Register: 29 February 2012. Randomised controlled trials of macrolide antibiotics compared to: placebo; another class of antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a different dose. Two authors independently extracted data and assessed risk of bias. Seven groups were contacted and provided additional data which were incorporated into the review. Ten of 31 studies identified were included (959 patients). Five studies with a low risk of bias examined azithromycin versus placebo and demonstrated consistent improvement in forced expiratory volume in one second over six months (mean difference at six months 3.97% (95% confidence interval 1.74% to 6.19%; n = 549, from four studies)). Patients treated with azithromycin were approximately twice as likely to be free of pulmonary exacerbation at six months, odds ratio 1.96 (95% confidence interval 1.15 to 3.33). With respect to secondary outcomes, there was a significant reduction in need for oral antibiotics and greater weight gain in those taking azithromycin. Adverse events were uncommon

Antibiotics in surgical treatment of acute abscesses.

PubMed Central

Blick, P W; Flowers, M W; Marsden, A K; Wilson, D H; Ghoneim, A T

1980-01-01

A four-way, double-blind, prospective trial of treatment of abscesses by incision, curettage, and primary closure with and without antibiotic cover (clindamycin injection before operation or capsules after operation, or both) was conducted. There was no appreciable difference in mean healing time between the patients given both the antibiotic injection and the antibiotic capsules and those given the injection and placebo capsules, whereas healing times in those given the placebo injection and antibiotic capsules or placebo only were appreciably longer. Four of the patients who were not given the antibiotic injection developed bacteraemia; one patient who was given the antibiotic injection also developed a bacteraemia, but this was caused by clindamycin-resistant bacteria. These results show that a single injection of an effective antibiotic before operation is sufficient to protect the patient against bacteraemia and permit optimum healing. PMID:7000250

Prophylactic antibiotics in acute pancreatitis: endless debate.

PubMed

Mourad, M M; Evans, Rpt; Kalidindi, V; Navaratnam, R; Dvorkin, L; Bramhall, S R

2017-02-01

INTRODUCTION The development of pancreatic infection is associated with the development of a deteriorating disease with subsequent high morbidity and mortality. There is agreement that in mild pancreatitis there is no need to use antibiotics; in severe pancreatitis it would appear to be a logical choice to use antibiotics to prevent secondary pancreatic infection and decrease associated mortality. MATERIALS AND METHODS A non-systematic review of current evidence, meta-analyses and randomized controlled trials was conducted to assess the role of prophylactic antibiotics in acute pancreatitis and whether it might improve morbidity and mortality in pancreatitis. RESULTS Mixed evidence was found to support and refute the role of prophylactic antibiotics in acute pancreatitis. Most studies have failed to demonstrate much benefit from its routine use. Data from our unit suggested little benefit of their routine use, and showed that the mortality of those treated with antibiotics was significantly higher compared with those not treated with antibiotics (9% vs 0%, respectively, P = 0.043). In addition, the antibiotic group had significantly higher morbidity (36% vs 5%, respectively, P = 0.002). CONCLUSIONS Antibiotics should be used in patients who develop sepsis, infected necrosis-related systemic inflammatory response syndrome, multiple organ dysfunction syndrome or pancreatic and extra-pancreatic infection. Despite the many other factors that should be considered, prompt antibiotic therapy is recommended once inflammatory markers are raised, to prevent secondary pancreatic infection. Unfortunately, there remain many unanswered questions regarding the indications for antibiotic administration and the patients who benefit from antibiotic treatment in acute pancreatitis.

Oral versus inhaled antibiotics for bronchiectasis.

PubMed

Spencer, Sally; Felix, Lambert M; Milan, Stephen J; Normansell, Rebecca; Goeminne, Pieter C; Chalmers, James D; Donovan, Tim

2018-03-27

Bronchiectasis is a chronic inflammatory disease characterised by a recurrent cycle of respiratory bacterial infections associated with cough, sputum production and impaired quality of life. Antibiotics are the main therapeutic option for managing bronchiectasis exacerbations. Evidence suggests that inhaled antibiotics may be associated with more effective eradication of infective organisms and a lower risk of developing antibiotic resistance when compared with orally administered antibiotics. However, it is currently unclear whether antibiotics are more effective when administered orally or by inhalation. To determine the comparative efficacy and safety of oral versus inhaled antibiotics in the treatment of adults and children with bronchiectasis. We identified studies through searches of the Cochrane Airways Group's Specialised Register (CAGR), which is maintained by the Information Specialist for the group. The Register contains trial reports identified through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched ClinicalTrials.gov and the WHO trials portal. We searched all databases in March 2018 and imposed no restrictions on language of publication. We planned to include studies which compared oral antibiotics with inhaled antibiotics. We would have considered short-term use (less than four weeks) for treating acute exacerbations separately from longer-term use as a prophylactic (4 weeks or more). We would have considered both intraclass and interclass comparisons. We planned to exclude studies if the participants received continuous or high-dose antibiotics immediately before the start of the trial, or if they have received a diagnosis of cystic fibrosis (CF), sarcoidosis, active allergic bronchopulmonary aspergillosis or active non-tuberculous Mycobacterial infection

Dissemination of health information through social networks: twitter and antibiotics.

PubMed

Scanfeld, Daniel; Scanfeld, Vanessa; Larson, Elaine L

2010-04-01

This study reviewed Twitter status updates mentioning "antibiotic(s)" to determine overarching categories and explore evidence of misunderstanding or misuse of antibiotics. One thousand Twitter status updates mentioning antibiotic(s) were randomly selected for content analysis and categorization. To explore cases of potential misunderstanding or misuse, these status updates were mined for co-occurrence of the following terms: "cold + antibiotic(s)," "extra + antibiotic(s)," "flu + antibiotic(s)," "leftover + antibiotic(s)," and "share + antibiotic(s)" and reviewed to confirm evidence of misuse or misunderstanding. Of the 1000 status updates, 971 were categorized into 11 groups: general use (n = 289), advice/information (n = 157), side effects/negative reactions (n = 113), diagnosis (n = 102), resistance (n = 92), misunderstanding and/or misuse (n = 55), positive reactions (n = 48), animals (n = 46), other (n = 42), wanting/needing (n = 19), and cost (n = 8). Cases of misunderstanding or abuse were identified for the following combinations: "flu + antibiotic(s)" (n = 345), "cold + antibiotic(s)" (n = 302), "leftover + antibiotic(s)" (n = 23), "share + antibiotic(s)" (n = 10), and "extra + antibiotic(s)" (n = 7). Social media sites offer means of health information sharing. Further study is warranted to explore how such networks may provide a venue to identify misuse or misunderstanding of antibiotics, promote positive behavior change, disseminate valid information, and explore how such tools can be used to gather real-time health data. 2010 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Persistence of antibiotic resistance: evaluation of a probiotic approach using antibiotic-sensitive Megasphaera elsdenii strains to prevent colonization of swine by antibiotic-resistant strains.

PubMed

Stanton, Thad B; Humphrey, Samuel B

2011-10-01

Megasphaera elsdenii is a lactate-fermenting, obligately anaerobic bacterium commonly present in the gastrointestinal tracts of mammals, including humans. Swine M. elsdenii strains were previously shown to have high levels of tetracycline resistance (MIC=64 to >256 μg/ml) and to carry mosaic (recombinant) tetracycline resistance genes. Baby pigs inherit intestinal microbiota from the mother sow. In these investigations we addressed two questions. When do M. elsdenii strains from the sow colonize baby pigs? Can five antibiotic-sensitive M. elsdenii strains administered intragastrically to newborn pigs affect natural colonization of the piglets by antibiotic-resistant (AR) M. elsdenii strains from the mother? M. elsdenii natural colonization of newborn pigs was undetectable (<10(4) CFU/g [wet weight] of feces) prior to weaning (20 days after birth). After weaning, all pigs became colonized (4 × 10(5) to 2 × 10(8) CFU/g feces). In a separate study, 61% (76/125) of M. elsdenii isolates from a gravid sow never exposed to antibiotics were resistant to chlortetracycline, ampicillin, or tylosin. The inoculation of the sow's offspring with mixtures of M. elsdenii antibiotic-sensitive strains prevented colonization of the offspring by maternal AR strains until at least 11 days postweaning. At 25 and 53 days postweaning, however, AR strains predominated. Antibiotic susceptibility phenotypes and single nucleotide polymorphism (SNP)-based identities of M. elsdenii isolated from sow and offspring were unexpectedly diverse. These results suggest that dosing newborn piglets with M. elsdenii antibiotic-sensitive strains delays but does not prevent colonization by maternal resistant strains. M. elsdenii subspecies diversity offers an explanation for the persistence of resistant strains in the absence of antibiotic selection.

Antibiotic research and development: business as usual?

PubMed

Harbarth, S; Theuretzbacher, U; Hackett, J

2015-01-01

The global burden of antibiotic resistance is tremendous and, without new anti-infective strategies, will continue to increase in the coming decades. Despite the growing need for new antibiotics, few pharmaceutical companies today retain active antibacterial drug discovery programmes. One reason is that it is scientifically challenging to discover new antibiotics that are active against the antibiotic-resistant bacteria of current clinical concern. However, the main hurdle is diminishing economic incentives. Increased global calls to minimize the overuse of antibiotics, the cost of meeting regulatory requirements and the low prices of currently marketed antibiotics are strong deterrents to antibacterial drug development programmes. New economic models that create incentives for the discovery of new antibiotics and yet reconcile these incentives with responsible antibiotic use are long overdue. DRIVE-AB is a €9.4 million public-private consortium, funded by the EU Innovative Medicines Initiative, that aims to define a standard for the responsible use of antibiotics and to develop, test and recommend new economic models to incentivize investment in producing new anti-infective agents. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Functional Repertoire of Antibiotic Resistance Genes in Antibiotic Manufacturing Effluents and Receiving Freshwater Sediments

PubMed Central

González-Plaza, Juan J.; Šimatović, Ana; Milaković, Milena; Bielen, Ana; Wichmann, Fabienne; Udiković-Kolić, Nikolina

2018-01-01

Environments polluted by direct discharges of effluents from antibiotic manufacturing are important reservoirs for antibiotic resistance genes (ARGs), which could potentially be transferred to human pathogens. However, our knowledge about the identity and diversity of ARGs in such polluted environments remains limited. We applied functional metagenomics to explore the resistome of two Croatian antibiotic manufacturing effluents and sediments collected upstream of and at the effluent discharge sites. Metagenomic libraries built from an azithromycin-production site were screened for resistance to macrolide antibiotics, whereas the libraries from a site producing veterinary antibiotics were screened for resistance to sulfonamides, tetracyclines, trimethoprim, and beta-lactams. Functional analysis of eight libraries identified a total of 82 unique, often clinically relevant ARGs, which were frequently found in clusters and flanked by mobile genetic elements. The majority of macrolide resistance genes identified from matrices exposed to high levels of macrolides were similar to known genes encoding ribosomal protection proteins, macrolide phosphotransferases, and transporters. Potentially novel macrolide resistance genes included one most similar to a 23S rRNA methyltransferase from Clostridium and another, derived from upstream unpolluted sediment, to a GTPase HflX from Emergencia. In libraries deriving from sediments exposed to lower levels of veterinary antibiotics, we found 8 potentially novel ARGs, including dihydrofolate reductases and beta-lactamases from classes A, B, and D. In addition, we detected 7 potentially novel ARGs in upstream sediment, including thymidylate synthases, dihydrofolate reductases, and class D beta-lactamase. Taken together, in addition to finding known gene types, we report the discovery of novel and diverse ARGs in antibiotic-polluted industrial effluents and sediments, providing a qualitative basis for monitoring the dispersal of ARGs

Antibiotics for treating septic abortion.

PubMed

Udoh, Atim; Effa, Emmanuel E; Oduwole, Olabisi; Okusanya, Babasola O; Okafo, Obiamaka

2016-07-01

A septic abortion refers to any abortion (spontaneous or induced) complicated by upper genital tract infection including endometritis or parametritis. The mainstay of treatment of septic abortion is antibiotic therapy alone or in combination with evacuation of retained products of conception. Regimens including broad-spectrum antibiotics are routinely recommended for treatment. However, there is no consensus on the most effective antibiotics alone or in combination to treat septic abortion. This review aimed to bridge this gap in knowledge to inform policy and practice. To review the effectiveness of various individual antibiotics or antibiotic regimens in the treatment of septic abortion. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and POPLINE using the following keywords: 'Abortion', 'septic abortion', 'Antibiotics', 'Infected abortion', 'postabortion infection'. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 19 April, 2016. We considered for inclusion randomised controlled trials (RCTs) and non-RCTs that compared antibiotic(s) to another antibiotic(s), irrespective of route of administration, dosage, and duration as well as studies comparing antibiotics alone with antibiotics in combination with other interventions such as dilation and curettage (D&C). Two review authors independently extracted data from included trials. We resolved disagreements through consultation with a third author. One review author entered extracted data into Review Manager 5.3, and a second review author cross-checked the entry for accuracy. We included 3 small RCTs involving 233 women that were conducted over 3 decades ago.Clindamycin did not differ significantly from penicillin plus chloramphenicol in reducing fever in all women (mean difference (MD) -12.30, 95% confidence interval (CI) -25.12 to 0.52; women = 77; studies = 1

Antibiotics and antibiotic resistance genes in global lakes: A review and meta-analysis.

PubMed

Yang, Yuyi; Song, Wenjuan; Lin, Hui; Wang, Weibo; Du, Linna; Xing, Wei

2018-04-10

Lakes are an important source of freshwater, containing nearly 90% of the liquid surface fresh water worldwide. Long retention times in lakes mean pollutants from discharges slowly circulate around the lakes and may lead to high ecological risk for ecosystem and human health. In recent decades, antibiotics and antibiotic resistance genes (ARGs) have been regarded as emerging pollutants. The occurrence and distribution of antibiotics and ARGs in global freshwater lakes are summarized to show the pollution level of antibiotics and ARGs and to identify some of the potential risks to ecosystem and human health. Fifty-seven antibiotics were reported at least once in the studied lakes. Our meta-analysis shows that sulfamethoxazole, sulfamerazine, sulfameter, tetracycline, oxytetracycline, erythromycin, and roxithromycin were found at high concentrations in both lake water and lake sediment. There is no significant difference in the concentration of sulfonamides in lake water from China and that from other countries worldwide; however, there was a significant difference in quinolones. Erythromycin had the lowest predicted hazardous concentration for 5% of the species (HC 5 ) and the highest ecological risk in lakes. There was no significant difference in the concentration of sulfonamide resistance genes (sul1 and sul2) in lake water and river water. There is surprisingly limited research on the role of aquatic biota in propagation of ARGs in freshwater lakes. As an environment that is susceptible to cumulative build-up of pollutants, lakes provide an important environment to study the fate of antibiotics and transport of ARGs with a broad range of niches including bacterial community, aquatic plants and animals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enabling techniques in the search for new antibiotics: Combinatorial biosynthesis of sugar-containing antibiotics.

PubMed

Park, Je Won; Nam, Sang-Jip; Yoon, Yeo Joon

2017-06-15

Nature has a talent for inventing a vast number of natural products, including hybrids generated by blending different scaffolds, resulting in a myriad of bioactive chemical entities. Herein, we review the highlights and recent trends (2010-2016) in the combinatorial biosynthesis of sugar-containing antibiotics where nature's structural diversification capabilities are exploited to enable the creation of new anti-infective and anti-proliferative drugs. In this review, we describe the modern combinatorial biosynthetic approaches for polyketide synthase-derived complex and aromatic polyketides, non-ribosomal peptide synthetase-directed lipo-/glycopeptides, aminoglycosides, nucleoside antibiotics, and alkaloids, along with their therapeutic potential. Finally, we present the feasible nexus between combinatorial biosynthesis, systems biology, and synthetic biology as a toolbox to provide new antibiotics that will be indispensable in the post-antibiotic era. Copyright © 2016 Elsevier Inc. All rights reserved.

Selective reporting of antibiotic susceptibility data improves the appropriateness of intended antibiotic prescriptions in urinary tract infections: a case-vignette randomised study.

PubMed

Coupat, C; Pradier, C; Degand, N; Hofliger, P; Pulcini, C

2013-05-01

The purpose of this investigation was to assess the impact of selective reporting of antibiotic susceptibility data on the appropriateness of intended documented antibiotic prescriptions in urinary tract infections (UTIs) among residents training in general practice. We conducted a randomised-controlled case-vignette study in three French universities using a questionnaire with four UTI vignettes. In each university, residents were randomly allocated to two groups: a control group with usual full-length reporting of antibiotic susceptibility data (25 antibiotics) and an intervention group with selective reporting of antibiotic susceptibility data (2 to 4 antibiotics only). 326/611 residents (53 %) participated in the survey, 157/305 (52 %) in the intervention group and 169/306 (55 %) in the control group. For all four UTI scenarios, selective reporting of antibiotic susceptibility data significantly improved the appropriateness of antibiotic prescriptions (absolute increase ranging from 7 to 41 %, depending on the vignette). The variety of antibiotic prescriptions was reduced in the intervention group, and cephalosporins and fluoroquinolones were less often prescribed. Among 325 respondents, 124 (38 %) declared being either not really or not at all at ease with antibiotic susceptibility data, whereas 112/157 (71 %) of the residents in the intervention group declared that selective reporting of antibiotic susceptibility data made their antibiotic choice easier. Selective reporting of antibiotic susceptibility data could be a promising strategy to improve antibiotic use in UTIs, as part of a multi-faceted antibiotic stewardship programme. Microbiology laboratories should be aware that they can have a significant influence on antibiotic use.

Emergence of antibiotic-resistant extremophiles (AREs).

PubMed

Gabani, Prashant; Prakash, Dhan; Singh, Om V

2012-09-01

Excessive use of antibiotics in recent years has produced bacteria that are resistant to a wide array of antibiotics. Several genetic and non-genetic elements allow microorganisms to adapt and thrive under harsh environmental conditions such as lethal doses of antibiotics. We attempt to classify these microorganisms as antibiotic-resistant extremophiles (AREs). AREs develop strategies to gain greater resistance to antibiotics via accumulation of multiple genes or plasmids that harbor genes for multiple drug resistance (MDR). In addition to their altered expression of multiple genes, AREs also survive by producing enzymes such as penicillinase that inactivate antibiotics. It is of interest to identify the underlying molecular mechanisms by which the AREs are able to survive in the presence of wide arrays of high-dosage antibiotics. Technologically, "omics"-based approaches such as genomics have revealed a wide array of genes differentially expressed in AREs. Proteomics studies with 2DE, MALDI-TOF, and MS/MS have identified specific proteins, enzymes, and pumps that function in the adaptation mechanisms of AREs. This article discusses the molecular mechanisms by which microorganisms develop into AREs and how "omics" approaches can identify the genetic elements of these adaptation mechanisms. These objectives will assist the development of strategies and potential therapeutics to treat outbreaks of pathogenic microorganisms in the future.

Distribution and degradation of common antibiotics and linkage to antibiotic resistance genes in the environment of Shenzhen, China

NASA Astrophysics Data System (ADS)

Sun, J.; Qiu, W.; Zheng, C.

2017-12-01

Antibiotics, as emerging contaminants, have been widely detected in environmental matrices in China and worldwide, such as wastewater treatment plants (WWTPs), hospital effluents, livestock farms, river water and sediment, soil, groundwater, and seawater. Thus, there exist significant concerns about their potential risks to human and ecosystem health. Compared to other countries, research on antibiotics in China is mainly focused on the watershed level, and there is a lack of information on emission inventory and environmental fate of antibiotics in China. In this study, we investigated the distribution of 21 frequently detected antibiotics in the five representative rivers in Shenzhen, China. Our monitoring results showed that the concentration of the 21 antibiotic contaminants in river waters and sediments ranges from 0.004ng/L to 0.378μg/L and from 0.005ng/kg to 2.089ng/kg, respectively. The data also revealed that the level of antibiotics in the five rivers exhibits strong temporal and spatial variations, and the antibiotic content in dry season is significantly higher than that in flood season. The bacterial resistance rates in sediments were found to be related to antibiotic usages, especially for those antibiotics used in the most recent period. Our degradation experiment results showed that the optimal conditions for the removal of enrofloxacin and pefloxacin were as follows: pH at 3 and the concentration of H2O2 and Fe2+ were 20mM and 0.25mM, respectively. This study can provide basic data useful for addressing the water environmental problems in Shenzhen and for dealing with national pollution control of antibiotics as emerging contaminants.

Magnetic separation of antibiotics by electrochemical magnetic seeding

NASA Astrophysics Data System (ADS)

Ihara, I.; Toyoda, K.; Beneragama, N.; Umetsu, K.

2009-03-01

Magnetic separation of several classes of antibiotics was investigated using electrochemical magnetic seeding. Electrocoagulation with a sacrificial anode followed by addition of magnetite particles was applied for the magnetic seeding of antibiotics. With electrochemical magnetic seeding using an iron anode, tetracycline antibiotics (oxytetracycline, chlortetracycline, doxycycline and tetracycline) and cephalosporin antibiotic (cefdinir) were rapidly removed from synthetic wastewater by magnetic separation using a neodymium magnet. Iron and aluminium anodes were suitable for magnetic seeding of the antibiotics. The results indicated that the ability of antibiotics to form strong complex with iron and aluminium allowed the higher removal by magnetic separation. This method would be appropriate for rapid treatment of antibiotics in wastewater.

Expedient antibiotics production: Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bienkowski, P.R.; Byers, C.H.; Lee, D.D.

The literature on the manufacture, separation and purification, and clinical uses of antibiotics was reviewed, and a bibliography of the pertinent material was completed. Five antimicrobial drugs, penicillin V and G, (and amoxicillin with clavulanic acid), Cephalexin (a cephalosporin), tetracycline and oxytetracycline, Bacitracin (topical), and sulfonamide (chemically produced) were identified for emergency production. Plants that manufacture antibiotics in the continental United States, Mexico, and Puerto Rico have been identified along with potential alternate sites such as those where SCP, enzyme, and fermentation ethanol are produced. Detailed process flow sheets and process descriptions have been derived from the literature and documented.more » This investigation revealed that a typical antibiotic-manufacturing facility is composed of two main sections: (1) a highly specialized, but generic, fermentation unit and (2) a multistep, complex separation and purification unit which is specific to a particular antibiotic product. The fermentation section requires specialized equipment for operation in a sterile environment which is not usually available in other industries. The emergency production of antibiotics under austere conditions will be feasible only if a substantial reduction in the complexity and degree of separation and purity normally required can be realized. Detailed instructions were developed to assist state and federal officials who would be directing the resumption of antibiotic production after a nuclear attack. 182 refs., 54 figs., 26 tabs.« less

Antibiotic stewardship through the EU project "ABS International".

PubMed

Allerberger, Franz; Frank, Annegret; Gareis, Roland

2008-01-01

The increasing problem of antimicrobial resistance requires implementation of antibiotic stewardship (ABS) programs. The project "ABS International--implementing antibiotic strategies for appropriate use of antibiotics in hospitals in member states of the European Union" was started in September 2006 in Austria, Belgium, the Czech Republic, Germany, Hungary, Italy, Poland, Slovenia and Slovakia. A training program for national ABS trainers was prepared and standard templates for ABS tools (antibiotic list, guides for antibiotic treatment and surgical prophylaxis, antibiotic-related organization) and valid process measures, as well as quality indicators for antibiotic use were developed. Specific ABS tools are being implemented in up to five healthcare facilities in each country. Although ABS International clearly focuses on healthcare institutions, future antimicrobial stewardship programs must also cover public education and antibiotic prescribing in primary care.

Antibiotic-containing polymers for localized, sustained drug delivery

PubMed Central

Stebbins, Nicholas D.; Ouimet, Michelle A.; Uhrich, Kathryn E.

2014-01-01

Many currently used antibiotics suffer from issues such as systemic toxicity, short half-life, and increased susceptibility to bacterial resistance. Although most antibiotic classes are administered systemically through oral or intravenous routes, a more efficient delivery system is needed. This review discusses the chemical conjugation of antibiotics to polymers, achieved by forming covalent bonds between antibiotics and a pre-existing polymer or by developing novel antibiotic-containing polymers. Through conjugating antibiotics to polymers, unique polymer properties can be taken advantage of. These polymeric antibiotics display controlled, sustained drug release and vary in antibiotic class type, synthetic method, polymer composition, bond lability, and antibacterial activity. The polymer synthesis, characterization, drug release, and antibacterial activities, if applicable, will be presented to offer a detailed overview of each system. PMID:24751888

An Algorithm Using Twelve Properties of Antibiotics to Find the Recommended Antibiotics, as in CPGs.

PubMed

Tsopra, R; Venot, A; Duclos, C

2014-01-01

Clinical Decision Support Systems (CDSS) incorporating justifications, updating and adjustable recommendations can considerably improve the quality of healthcare. We propose a new approach to the design of CDSS for empiric antibiotic prescription, based on implementation of the deeper medical reasoning used by experts in the development of clinical practice guidelines (CPGs), to deduce the recommended antibiotics. We investigated two methods ("exclusion" versus "scoring") for reproducing this reasoning based on antibiotic properties. The "exclusion" method reproduced expert reasoning the more accurately, retrieving the full list of recommended antibiotics for almost all clinical situations. This approach has several advantages: (i) it provides convincing explanations for physicians; (ii) updating could easily be incorporated into the CDSS; (iii) it can provide recommendations for clinical situations missing from CPGs.

Effect of temperature on sulfonamide antibiotics degradation, and on antibiotic resistance determinants and hosts in animal manures.

PubMed

Lin, Hui; Zhang, Jin; Chen, Hongjin; Wang, Jianmei; Sun, Wanchun; Zhang, Xin; Yang, Yuyi; Wang, Qiang; Ma, Junwei

2017-12-31

Animal manure is a main reservoir of antibiotic residues and antibiotic resistance. Here, the effect of temperature on sulfonamide antibiotics (SAs), sulfonamide-resistant (SR) genes/bacteria was investigated by aerobically incubating swine and chicken manures at different temperatures. In swine manure, the SAs concentration declined with increasing temperature, with a minimum at 60°C. In chicken manure, the greatest degradation of SAs was noted at 30°C. The reduction of relative abundance of antibiotic resistance genes (ARGs) and sul-positive hosts in swine manure was more pronounced during thermophilic than mesospheric incubation; neither temperature conditions effectively reduced these parameters in chicken manure. The relationship between the residual levels/distribution profiles of SAs, ARGs (sul1, sul2 and intI1), cultivable SR bacteria and sul-positive hosts was further established. The antibiotic residual profile, rather than antibiotic concentration, acted as an important factor in the prevalence of ARGs and sul-positive hosts in manure. Corynebacterium and Leucobacter from the phylum Actinobacteria tend to be main carriers of sul1 and intI1; the relative abundance of sul2 was significantly correlated with the relative abundance of cultivable SR bacteria. Overall, differences in resistant bacterial communities also constitute a dominant factor affecting ARG variation. This study contributes to management options for reducing the pollution of antibiotics and antibiotic resistance within manure. Copyright © 2017 Elsevier B.V. All rights reserved.

Antibiotics: Misuse Puts You and Others at Risk

MedlinePlus

... those bacteria are said to be antibiotic resistant. Antibiotic resistance is one of the world's most pressing health ... misuse of antibiotics are key factors contributing to antibiotic resistance. The general public, doctors and hospitals all play ...

Efficacy of prophylactic probiotics in combination with antibiotics versus antibiotics alone for colorectal surgery: A meta-analysis of randomized controlled trials.

PubMed

Wu, Xiang-Dong; Xu, Wei; Liu, Meng-Meng; Hu, Ke-Jia; Sun, Ya-Ying; Yang, Xue-Fei; Zhu, Gui-Qi; Wang, Zi-Wei; Huang, Wei

2018-03-24

This meta-analysis aimed to determine whether prophylactic probiotics in combination with antibiotics are superior to antibiotics alone in the prevention of surgical site infection (SSI) after colorectal surgery. Fourteen trials involving 1524 participants were included. Compared with antibiotics alone, prophylactic probiotics in combination with antibiotics reduced the risk of SSI as well as other complications, shortened the cumulative duration of antibiotic therapy. Current evidence suggested that probiotics in combination with antibiotics could be recommended. © 2018 Wiley Periodicals, Inc.

Mechanisms of Antibiotic Resistance

PubMed Central

Munita, Jose M.; Arias, Cesar A.

2015-01-01

Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

Antibiotic Dosing in Continuous Renal Replacement Therapy.

PubMed

Shaw, Alexander R; Mueller, Bruce A

2017-07-01

Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Probing minority population of antibiotic-resistant bacteria.

PubMed

Huang, Tianxun; Zheng, Yan; Yan, Ya; Yang, Lingling; Yao, Yihui; Zheng, Jiaxin; Wu, Lina; Wang, Xu; Chen, Yuqing; Xing, Jinchun; Yan, Xiaomei

2016-06-15

The evolution and spread of antibiotic-resistant pathogens has become a major threat to public health. Advanced tools are urgently needed to quickly diagnose antibiotic-resistant infections to initiate appropriate treatment. Here we report the development of a highly sensitive flow cytometric method to probe minority population of antibiotic-resistant bacteria via single cell detection. Monoclonal antibody against TEM-1 β-lactamase and Alexa Fluor 488-conjugated secondary antibody were used to selectively label resistant bacteria green, and nucleic acid dye SYTO 62 was used to stain all the bacteria red. A laboratory-built high sensitivity flow cytometer (HSFCM) was applied to simultaneously detect the side scatter and dual-color fluorescence signals of single bacteria. By using E. coli JM109/pUC19 and E. coli JM109 as the model systems for antibiotic-resistant and antibiotic-susceptible bacteria, respectively, as low as 0.1% of antibiotic-resistant bacteria were accurately quantified. By monitoring the dynamic population change of a bacterial culture with the administration of antibiotics, we confirmed that under the antimicrobial pressure, the original low population of antibiotic-resistant bacteria outcompeted susceptible strains and became the dominant population after 5hours of growth. Detection of antibiotic-resistant infection in clinical urine samples was achieved without cultivation, and the bacterial load of susceptible and resistant strains can be faithfully quantified. Overall, the HSFCM-based quantitative method provides a powerful tool for the fundamental studies of antibiotic resistance and holds the potential to provide rapid and precise guidance in clinical therapies. Copyright © 2016 Elsevier B.V. All rights reserved.

Antibiotic efficacy is linked to bacterial cellular respiration

PubMed Central

Lobritz, Michael A.; Belenky, Peter; Porter, Caroline B. M.; Gutierrez, Arnaud; Yang, Jason H.; Schwarz, Eric G.; Dwyer, Daniel J.; Khalil, Ahmad S.; Collins, James J.

2015-01-01

Bacteriostatic and bactericidal antibiotic treatments result in two fundamentally different phenotypic outcomes—the inhibition of bacterial growth or, alternatively, cell death. Most antibiotics inhibit processes that are major consumers of cellular energy output, suggesting that antibiotic treatment may have important downstream consequences on bacterial metabolism. We hypothesized that the specific metabolic effects of bacteriostatic and bactericidal antibiotics contribute to their overall efficacy. We leveraged the opposing phenotypes of bacteriostatic and bactericidal drugs in combination to investigate their activity. Growth inhibition from bacteriostatic antibiotics was associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics was associated with accelerated respiration. In combination, suppression of cellular respiration by the bacteriostatic antibiotic was the dominant effect, blocking bactericidal killing. Global metabolic profiling of bacteriostatic antibiotic treatment revealed that accumulation of metabolites involved in specific drug target activity was linked to the buildup of energy metabolites that feed the electron transport chain. Inhibition of cellular respiration by knockout of the cytochrome oxidases was sufficient to attenuate bactericidal lethality whereas acceleration of basal respiration by genetically uncoupling ATP synthesis from electron transport resulted in potentiation of the killing effect of bactericidal antibiotics. This work identifies a link between antibiotic-induced cellular respiration and bactericidal lethality and demonstrates that bactericidal activity can be arrested by attenuated respiration and potentiated by accelerated respiration. Our data collectively show that antibiotics perturb the metabolic state of bacteria and that the metabolic state of bacteria impacts antibiotic efficacy. PMID:26100898

Release of antibiotics from collagen dressing.

PubMed

Grzybowski, J; Antos-Bielska, M; Ołdak, E; Trafny, E A

1997-01-01

Our new collagen dressing has been developed recently. Three types (A, B, and C) of the dressing were prepared in this study. Each type contained bacitracin, neomycin or colistin. The antibiotic was input into: i. collagen sponge (CS)--type A, ii. layer of limited hydrophobicity (LLH)--type B, and iii. into both CS and LLH layers--type C. The final concentration of the antibiotic that resulted from the loading level was 2 mg/cm2 for the dressings of type A and B and 4 mg/cm2 for the dressing of type C. The antibiotics were then extracted from the pieces of dressings for two days through dialysis membrane. Susceptibility of 54 bacterial strains (S. aureus, P. aeruginosa, and Acinetobacter) isolated from burn wounds were tested to the three antibiotics used for preparation of the dressings. The results of the study evidenced that efficiency of released of antibiotics into the extracts depended on the kind of antibiotic and on the type of dressing. The concentration of the antibiotics proved to be much higher than MIC90 values of the bacterial isolates tested in respect to their susceptibility. The dressing containing mixture of the three antibiotics in two layers--CS and LLH is now considered as potentially effective for care of infected wounds. It may be useful for the treatment of infected wounds or for profilaxis of contaminated wounds, ensuring: i. sufficient antimicrobial activity in wound, and ii. optimal wound environment for the presence of collagenic biomaterial on the damaged tissue.

Ready for a world without antibiotics? The Pensières Antibiotic Resistance Call to Action

PubMed Central

2012-01-01

Resistance to antibiotics has increased dramatically over the past few years and has now reached a level that places future patients in real danger. Microorganisms such as Escherichia coli and Klebsiella pneumoniae, which are commensals and pathogens for humans and animals, have become increasingly resistant to third-generation cephalosporins. Moreover, in certain countries, they are also resistant to carbapenems and therefore susceptible only to tigecycline and colistin. Resistance is primarily attributed to the production of beta-lactamase genes located on mobile genetic elements, which facilitate their transfer between different species. In some rare cases, Gram-negative rods are resistant to virtually all known antibiotics. The causes are numerous, but the role of the overuse of antibiotics in both humans and animals is essential, as well as the transmission of these bacteria in both the hospital and the community, notably via the food chain, contaminated hands, and between animals and humans. In addition, there are very few new antibiotics in the pipeline, particularly for Gram-negative bacilli. The situation is slightly better for Gram-positive cocci as some potent and novel antibiotics have been made available in recent years. A strong and coordinated international programme is urgently needed. To meet this challenge, 70 internationally recognized experts met for a two-day meeting in June 2011 in Annecy (France) and endorsed a global call to action ("The Pensières Antibiotic Resistance Call to Action"). Bundles of measures that must be implemented simultaneously and worldwide are presented in this document. In particular, antibiotics, which represent a treasure for humanity, must be protected and considered as a special class of drugs. PMID:22958833

Tackling antibiotic resistance: the environmental framework.

PubMed

Berendonk, Thomas U; Manaia, Célia M; Merlin, Christophe; Fatta-Kassinos, Despo; Cytryn, Eddie; Walsh, Fiona; Bürgmann, Helmut; Sørum, Henning; Norström, Madelaine; Pons, Marie-Noëlle; Kreuzinger, Norbert; Huovinen, Pentti; Stefani, Stefania; Schwartz, Thomas; Kisand, Veljo; Baquero, Fernando; Martinez, José Luis

2015-05-01

Antibiotic resistance is a threat to human and animal health worldwide, and key measures are required to reduce the risks posed by antibiotic resistance genes that occur in the environment. These measures include the identification of critical points of control, the development of reliable surveillance and risk assessment procedures, and the implementation of technological solutions that can prevent environmental contamination with antibiotic resistant bacteria and genes. In this Opinion article, we discuss the main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment.

Antibiotics: MedlinePlus Health Topic

MedlinePlus

... or not using them properly, can add to antibiotic resistance . This happens when bacteria change and become able ... ports Pseudomembranous colitis Sensitivity analysis Related Health Topics Antibiotic Resistance Bacterial Infections Medicines National Institutes of Health The ...

Antibiotic prophylaxis for operative vaginal delivery.

PubMed

Liabsuetrakul, Tippawan; Choobun, Thanapan; Peeyananjarassri, Krantarat; Islam, Q Monir

2017-08-05

Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps deliveries, or both. We searched Cochrane Pregnancy and Childbirth's Trials Register (12 July 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (12 July 2017) and reference lists of retrieved studies. All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Two review authors assessed trial eligibility and methodological quality. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. We assessed methodological quality of the one included trial using the GRADE approach. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. The trial compared the antibiotic intravenous cefotetan after cord clamping compared with no treatment. This trial reported only two out of the nine outcomes specified in this review. Seven women in the group

Correlates of parental antibiotic knowledge, demand, and reported use.

PubMed

Kuzujanakis, Marianne; Kleinman, Ken; Rifas-Shiman, Sheryl; Finkelstein, Jonathan A

2003-01-01

Clinicians cite parental misconceptions and requests for antibiotics as reasons for inappropriate prescribing. To identify misconceptions regarding antibiotics and predictors of parental demand for antibiotics and to determine if parental knowledge and attitudes are associated with use. Survey of parents in 16 Massachusetts communities. Domains included antibiotic-related knowledge, attitudes about antibiotics, antibiotic use during a 12-month period, demographics, and access to health information. Bivariate and multivariate analyses evaluated predictors of knowledge and proclivity to demand antibiotics. A multivariate model evaluated the associations of knowledge, demand, and demographic factors with parent-reported antibiotic use. A total of 1106 surveys were returned (response rates: 54% and 32% for commercially-insured and Medicaid-insured families). Misconceptions were common regarding bronchitis (92%) and green nasal discharge (78%). Two hundred sixty-five (24%) gave responses suggesting a proclivity to demand antibiotics. Antibiotic knowledge was associated with increased parental age and education, having more than 1 child, white race, and receipt of media information on resistance. Factors associated with a proclivity to demand antibiotics included decreased knowledge, pressure from day-care settings, lack of alternatives offered by clinicians, and lack of access to media information. Among all respondents, reported antibiotic use was associated with younger child age and day-care attendance. Among Medicaid-insured children only, less antibiotic knowledge and tendency to demand antibiotics were associated with higher rates of antibiotic use. Misconceptions regarding antibiotic use are widespread and potentially modifiable by clinicians and media sources. Particular attention should be paid to Medicaid-insured patients in whom such misconceptions may contribute to inappropriate prescribing.

An Algorithm Using Twelve Properties of Antibiotics to Find the Recommended Antibiotics, as in CPGs

PubMed Central

Tsopra, R.; Venot, A.; Duclos, C.

2014-01-01

Background Clinical Decision Support Systems (CDSS) incorporating justifications, updating and adjustable recommendations can considerably improve the quality of healthcare. We propose a new approach to the design of CDSS for empiric antibiotic prescription, based on implementation of the deeper medical reasoning used by experts in the development of clinical practice guidelines (CPGs), to deduce the recommended antibiotics. Methods We investigated two methods (“exclusion” versus “scoring”) for reproducing this reasoning based on antibiotic properties. Results The “exclusion” method reproduced expert reasoning the more accurately, retrieving the full list of recommended antibiotics for almost all clinical situations. Discussion This approach has several advantages: (i) it provides convincing explanations for physicians; (ii) updating could easily be incorporated into the CDSS; (iii) it can provide recommendations for clinical situations missing from CPGs. PMID:25954422

[Historical and Hygienic Aspects on Roles of Quality Requirements for Antibiotic Products in Japan: Part 1--Development of Antibiotic Products].

PubMed

Yagisawa, Morimasa; Foster, Patrick J; Kurokawa, Tatsuo

2015-01-01

Antibiotic products have contributed greatly to keep Japanese people healthy by controlling lethal infections. In the early days, antibiotics such as penicillin and streptomycin were produced using microbial fermentation processes. Therefore, the component ratio of the active element and related substances varied lot by lot. For the purpose of efficacy and assuring safety, minimum requirements for penicillin and streptomycin products were enacted. Both variations and the number of clinically available antibiotic products have increased due to the pharmaceutical development of novel natural antibiotics. In addition, semi-synthetic derivatives of various antibiotics have been developed for the purpose of enhancing antimicrobial activity or improving pharmacological properties. As a result, 202 entities of antibiotic products have been approved and used clinically as of 2012. We conducted a detailed investigation of the progress made in the field of antibiotic products, and analyzed the characteristics of those belonging to each class of antibiotics by means of setting up a system of classification that reflects clinical applications. This report is intended to serve as an introduction to our series of investigations into the role and influence of quality requirements on development of antibacterial antibiotic products in Japan. As described here, the general view of antibacterial antibiotic products spanning a time frame of 67 years in Japan might serve as an ideal reference for future reports.

Antibiotics in agroecosystems: Introduction to the special section

USDA-ARS?s Scientific Manuscript database

The presence of antibiotic drug residues, antibiotic resistant bacteria, and antibiotic resistance genes in agroecosystems has become a significant area of research in recent years, and is a growing public health concern. While antibiotics are utilized for human medicine and agricultural practices, ...

[Potentialization of antibiotics by lytic enzymes].

PubMed

Brisou, J; Babin, P; Babin, R

1975-01-01

Few lytic enzymes, specially papaine and lysozyme, acting on the membrane and cell wall structures facilitate effects of bacitracine, streptomycine and other antibiotics. Streptomycino resistant strains became sensibles to this antibiotic after contact with papaine and lysozyme. The results of tests in physiological suspensions concern only the lytic activity of enzymes. The results on nutrient medium concern together lytic, and antibiotic activities.

[Antibiotic resistance: A global crisis].

PubMed

Alós, Juan-Ignacio

2015-12-01

The introduction of antibiotics into clinical practice represented one of the most important interventions for the control of infectious diseases. Antibiotics have saved millions of lives and have also brought a revolution in medicine. However, an increasing threat has deteriorated the effectiveness of these drugs, that of bacterial resistance to antibiotics, which is defined here as the ability of bacteria to survive in antibiotic concentrations that inhibit/kill others of the same species. In this review some recent and important examples of resistance in pathogens of concern for mankind are mentioned. It is explained, according to present knowledge, the process that led to the current situation in a short time, evolutionarily speaking. It begins with the resistance genes, continues with clones and genetic elements involved in the maintenance and dissemination, and ends with other factors that contribute to its spread. Possible responses to the problem are also reviewed, with special reference to the development of new antibiotics. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Antibiotics: natural products essential to human health.

PubMed

Demain, Arnold L

2009-11-01

For more than 50 years, natural products have served us well in combating infectious bacteria and fungi. Microbial and plant secondary metabolites helped to double our life span during the 20th century, reduced pain and suffering, and revolutionized medicine. Most antibiotics are either (i) natural products of microorganisms, (ii) semi-synthetically produced from natural products, or (iii) chemically synthesized based on the structure of the natural products. Production of antibiotics began with penicillin in the late 1940s and proceeded with great success until the 1970-1980s when it became harder and harder to discover new and useful products. Furthermore, resistance development in pathogens became a major problem, which is still with us today. In addition, new pathogens are continually emerging and there are still bacteria that are not eliminated by any antibiotic, e.g., Pseudomonas aeruginosa. In addition to these problems, many of the major pharmaceutical companies have abandoned the antibiotic field, leaving much of the discovery efforts to small companies, new companies, and the biotechnology industries. Despite these problems, development of new antibiotics has continued, albeit at a much lower pace than in the last century. We have seen the (i) appearance of newly discovered antibiotics (e.g., candins), (ii) development of old but unutilized antibiotics (e.g., daptomycin), (iii) production of new semi-synthetic versions of old antibiotics (e.g., glycylcyclines, streptogrammins), as well as the (iv) very useful application of old but underutilized antibiotics (e.g., teicoplanin).

Repairing the broken market for antibiotic innovation.

PubMed

Outterson, Kevin; Powers, John H; Daniel, Gregory W; McClellan, Mark B

2015-02-01

Multidrug-resistant bacterial diseases pose serious and growing threats to human health. While innovation is important to all areas of health research, it is uniquely important in antibiotics. Resistance destroys the fruit of prior research, making it necessary to constantly innovate to avoid falling back into a pre-antibiotic era. But investment is declining in antibiotics, driven by competition from older antibiotics, the cost and uncertainty of the development process, and limited reimbursement incentives. Good public health practices curb inappropriate antibiotic use, making return on investment challenging in payment systems based on sales volume. We assess the impact of recent initiatives to improve antibiotic innovation, reflecting experience with all sixty-seven new molecular entity antibiotics approved by the Food and Drug Administration since 1980. Our analysis incorporates data and insights derived from several multistakeholder initiatives under way involving governments and the private sector on both sides of the Atlantic. We propose three specific reforms that could revitalize innovations that protect public health, while promoting long-term sustainability: increased incentives for antibiotic research and development, surveillance, and stewardship; greater targeting of incentives to high-priority public health needs, including reimbursement that is delinked from volume of drug use; and enhanced global collaboration, including a global treaty. Project HOPE—The People-to-People Health Foundation, Inc.

Surveys of public knowledge and attitudes with regard to antibiotics in Poland: Did the European Antibiotic Awareness Day campaigns change attitudes?

PubMed

Mazińska, Beata; Strużycka, Izabela; Hryniewicz, Waleria

2017-01-01

Antimicrobial resistance is a global public health problem. Monitoring the level of knowledge regarding antibiotics is a part of the European Union Community strategy against antimicrobial resistance. To assess knowledge by the general public in Poland regarding antibiotics, AMR, and the impact of the European Antibiotic Awareness Day campaigns. The repeated cross-sectional study was developed and carried out among the general public in Poland (in 5 waves between 2009 and 2011, embracing a total of 5004 respondents). The survey was based on a self-designed questionnaire, and carried out by Millward Brown SMG/KRC, using Computer Assisted Telephone Interviews (CATI). A high percentage of Polish adults had used antibiotics within the 12 months preceding their participation in the study (38%). Statistically relevant differences were observed regarding the respondents' gender, age, education and employment status. The majority of the antibiotics used were prescribed by physicians (90%). In all five waves, 3% of the respondents purchased an antibiotic without a prescription. Prescriptions were mostly obtained from a general practitioner. The prevailing reasons for taking antibiotics were the common cold, sore throat, cough and flu. Approximately 40% of the respondents expected a prescription for an antibiotic against the flu. The vast majority knew that antibiotics kill bacteria (80%) but at the same time 60% of respondents believed antibiotics kill viruses. Physicians, pharmacists, hospital staff and nurses were mentioned as the most trustworthy sources of information. A third of the respondents declared to have come across information on the prudent use of antibiotics in the preceding 12 months. In the fifth wave, nearly half of the participants (48%), who had come across information about antibiotics in the preceding 12 months declared that the information resulted in a change in their attitude towards antibiotic use. The survey generated information about the

Surveys of public knowledge and attitudes with regard to antibiotics in Poland: Did the European Antibiotic Awareness Day campaigns change attitudes?

PubMed Central

Mazińska, Beata; Strużycka, Izabela; Hryniewicz, Waleria

2017-01-01

Background Antimicrobial resistance is a global public health problem. Monitoring the level of knowledge regarding antibiotics is a part of the European Union Community strategy against antimicrobial resistance. Objective To assess knowledge by the general public in Poland regarding antibiotics, AMR, and the impact of the European Antibiotic Awareness Day campaigns. Methods The repeated cross-sectional study was developed and carried out among the general public in Poland (in 5 waves between 2009 and 2011, embracing a total of 5004 respondents). The survey was based on a self-designed questionnaire, and carried out by Millward Brown SMG/KRC, using Computer Assisted Telephone Interviews (CATI). Results A high percentage of Polish adults had used antibiotics within the 12 months preceding their participation in the study (38%). Statistically relevant differences were observed regarding the respondents’ gender, age, education and employment status. The majority of the antibiotics used were prescribed by physicians (90%). In all five waves, 3% of the respondents purchased an antibiotic without a prescription. Prescriptions were mostly obtained from a general practitioner. The prevailing reasons for taking antibiotics were the common cold, sore throat, cough and flu. Approximately 40% of the respondents expected a prescription for an antibiotic against the flu. The vast majority knew that antibiotics kill bacteria (80%) but at the same time 60% of respondents believed antibiotics kill viruses. Physicians, pharmacists, hospital staff and nurses were mentioned as the most trustworthy sources of information. A third of the respondents declared to have come across information on the prudent use of antibiotics in the preceding 12 months. In the fifth wave, nearly half of the participants (48%), who had come across information about antibiotics in the preceding 12 months declared that the information resulted in a change in their attitude towards antibiotic use. Conclusion

Antibiotic-resistant bacteria in the guts of insects feeding on plants: prospects for discovering plant-derived antibiotics.

PubMed

Ignasiak, Katarzyna; Maxwell, Anthony

2017-12-01

Although plants produce many secondary metabolites, currently none of these are commercial antibiotics. Insects feeding on specific plants can harbour bacterial strains resistant to known antibiotics suggesting that compounds in the plant have stimulated resistance development. We sought to determine whether the occurrence of antibiotic-resistant bacteria in insect guts was a widespread phenomenon, and whether this could be used as a part of a strategy to identify antibacterial compounds from plants. Six insect/plant pairs were selected and the insect gut bacteria were identified and assessed for antibiotic susceptibilities compared with type strains from culture collections. We found that the gut strains could be more or less susceptible to antibiotics than the type strains, or show no differences. Evidence of antibacterial activity was found in the plant extracts from five of the six plants, and, in one case Catharanthus roseus (Madagascar Periwinkle), compounds with antibacterial activity were identified. Bacterial strains isolated from insect guts show a range of susceptibilities to antibiotics suggesting a complex interplay between species in the insect gut microbiome. Extracts from selected plants can show antibacterial activity but it is not easy to isolate and identify the active components. We found that vindoline, present in Madagascar Periwinkle extracts, possessed moderate antibacterial activity. We suggest that plant-derived antibiotics are a realistic possibility given the advances in genomic and metabolomic methodologies.

Australian consumer perspectives, attitudes and behaviours on antibiotic use and antibiotic resistance: a qualitative study with implications for public health policy and practice.

PubMed

Lum, Elaine P M; Page, Katie; Nissen, Lisa; Doust, Jenny; Graves, Nicholas

2017-10-10

Consumers receive over 27 million antibiotic prescriptions annually in Australian primary healthcare. Hence, consumers are a key group to engage in the fight against antibiotic resistance. There is a paucity of research pertaining to consumers in the Australian healthcare environment. This study aimed to investigate the perspectives, attitudes and behaviours of Australian consumers on antibiotic use and antibiotic resistance, to inform national programs for reducing inappropriate antibiotic consumption. Semi-structured interviews with 32 consumers recruited via convenience and snowball sampling from a university population in South East Queensland. Interview transcripts were deductively and inductively coded. Main themes were identified using iterative thematic analysis. Three themes emerged from the analysis, to elucidate factors affecting antibiotic use: (a) prescription type; (b) consumer attitudes, behaviours, skills and knowledge; and (c) consumer engagement with antibiotic resistance. Consumers held mixed views regarding the use of delayed antibiotic prescriptions, and were often not made aware of the use of repeat antibiotic prescriptions. Consumers with regular general practitioners were more likely to have shared expectations regarding minimising the use of antibiotics. Even so, advice or information mediated by general practitioners was influential with all consumers; and helped to prevent inappropriate antibiotic use behaviours. Consumers were not aware of the free Return of Unwanted Medicines service offered by pharmacies and disposed of leftover antibiotics through household waste. To engage with mitigating antibiotic resistance, consumers required specific information. Previous public health campaigns raising awareness of antibiotics were largely not seen by this sample of consumers. Australian consumers have specific information needs regarding prescribed antibiotics to enable appropriate antibiotic use behaviours. Consumers also have expectations

Antibiotics for acute maxillary sinusitis in adults.

PubMed

Ahovuo-Saloranta, Anneli; Rautakorpi, Ulla-Maija; Borisenko, Oleg V; Liira, Helena; Williams, John W; Mäkelä, Marjukka

2014-02-11

Sinusitis is one of the most common diagnoses among adults in ambulatory care, accounting for 15% to 21% of all adult outpatient antibiotic prescriptions. However, the role of antibiotics for sinusitis is controversial. To assess the effects of antibiotics in adults with acute maxillary sinusitis by comparing antibiotics with placebo, antibiotics from different classes and the side effects of different treatments. We searched CENTRAL 2013, Issue 2, MEDLINE (1946 to March week 3, 2013), EMBASE (1974 to March 2013), SIGLE (OpenSIGLE, later OpenGrey (accessed 15 January 2013)), reference lists of the identified trials and systematic reviews of placebo-controlled studies. We also searched for ongoing trials via ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). We imposed no language or publication restrictions. Randomised controlled trials (RCTs) comparing antibiotics with placebo or antibiotics from different classes for acute maxillary sinusitis in adults. We included trials with clinically diagnosed acute sinusitis, confirmed or not by imaging or bacterial culture. Two review authors independently screened search results, extracted data and assessed trial quality. We calculated risk ratios (RRs) for differences between intervention and control groups in whether the treatment failed or not. All measures are presented with 95% confidence intervals (CIs). We conducted the meta-analyses using either the fixed-effect or random-effects model. In meta-analyses of the placebo-controlled studies, we combined data across antibiotic classes. Primary outcomes were clinical failure rates at 7 to 15 days and 16 to 60 days follow-up. We used GRADEpro to assess the quality of the evidence. We included 63 studies in this updated review; nine placebo-controlled studies involving 1915 participants (seven of the studies clearly conducted in primary care settings) and 54 studies comparing different classes of antibiotics (10 different comparisons

Bacterial cheating limits the evolution of antibiotic resistance

NASA Astrophysics Data System (ADS)

Chao, Hui Xiao; Datta, Manoshi; Yurtsev, Eugene; Gore, Jeff

2011-03-01

The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain--which does not contribute to breaking down the antibiotic--may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we experimentally find that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors found in nature.

Antibiotic Policies and Utilization in Oregon Hospice Programs.

PubMed

Novak, Rachel L; Noble, Brie N; Fromme, Erik K; Tice, Michael O; McGregor, Jessina C; Furuno, Jon P

2016-09-01

Antibiotics are frequently used in hospice care, despite limited data on safety and effectiveness in this patient population. We surveyed Oregon hospice programs on antibiotic policies and prescribing practices. Among 39 responding hospice programs, the median reported proportion of current census using antibiotics was 10% (interquartile range = 3.5%-20.0%). Approximately 31% of responding hospice programs had policies for antibiotic initiation, 17% of hospice programs had policies for antibiotic discontinuation, and 95% of hospice programs had policies for managing drug interactions. Diarrhea, nausea/vomiting, and yeast infections were the most frequently reported antibiotic-associated adverse events, occurring "sometimes" or "often" among 62%, 47%, and 62% of respondents, respectively. In conclusion, less than a third of participating hospice programs reported having a policy for antibiotic initiation and even less frequently a policy for discontinuation. More data are needed on the risks and benefits of antibiotic use in hospice care to inform these policies and optimize outcomes in this vulnerable patient population. © The Author(s) 2015.

Inhaled Antibiotics for Ventilator-Associated Infections.

PubMed

Palmer, Lucy B

2017-09-01

Multidrug-resistant organisms are creating a challenge for physicians treating the critically ill. As new antibiotics lag behind the emergence of worsening resistance, intensivists in countries with high rates of extensively drug-resistant bacteria are turning to inhaled antibiotics as adjunctive therapy. These drugs can provide high concentrations of drug in the lung that could not be achieved with intravenous antibiotics without significant systemic toxicity. This article summarizes current evidence describing the use of inhaled antibiotics for the treatment of bacterial ventilator-associated pneumonia and ventilator-associated tracheobronchitis. Preliminary data suggest aerosolized antimicrobials may effectively treat resistant pathogens with high minimum inhibitory concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.

Endoscopic sinus surgery reduces antibiotic utilization in rhinosinusitis

PubMed Central

Bhandarkar, Naveen D.; Mace, Jess C.; Smith, Timothy L.

2011-01-01

Background Antibiotics are a mainstay of treatment for chronic rhinosinusitis (CRS) and recurrent acute rhinosinusitis (RARS). Although quality-of-life outcomes following endoscopic sinus surgery (ESS) have been previously studied, the change in antibiotic utilization following ESS is less well known. Objective We aimed to determine the effect of ESS on antibiotic utilization in CRS and RARS. Methods A multi-institutional, prospective cohort of patients with CRS and RARS was enrolled between January, 2001 and January, 2009. Patients completed the medication subscale of the Chronic Sinusitis Survey, and the Wilcoxon signed-rank test was used to compare differences in the overall reported time of antibiotic between preoperative and postoperative time points. Results 503 patients were followed for an average 17.3 months. Overall, patients reported a 57.2% reduction in time on antibiotics following ESS. The majority of patients (60.4%) reported significantly less antibiotic utilization after ESS (p<0.001) consisting of an 83.7% reduction in the time on antibiotics. Subgroup analysis also revealed a significant reduction in antibiotic utilization for patients with and without nasal polyposis (59.0% and 58.2%; both p<0.001) as well as RARS (61.2%; p=0.001). Conclusion ESS significantly reduces antibiotic utilization for CRS and RARS. This finding demonstrates potential for lower health care expenditures related to antibiotics, as well as reduced risk of both antibiotic related morbidity and development of bacterial resistance. PMID:21666846

Intraventricular antibiotics for bacterial meningitis in neonates.

PubMed

Shah, Sachin S; Ohlsson, Arne; Shah, Vibhuti S

2012-07-11

Neonatal meningitis may be caused by bacteria, especially gram-negative bacteria, which are difficult to eradicate from the cerebrospinal fluid (CSF) using safe doses of antibiotics. In theory, intraventricular administration of antibiotics would produce higher antibiotic concentrations in the CSF than intravenous administration alone, and eliminate the bacteria more quickly. However, ventricular taps may cause harm. To assess the effectiveness and safety of intraventricular antibiotics (with or without intravenous antibiotics) in neonates with meningitis (with or without ventriculitis) as compared to treatment with intravenous antibiotics alone. The Cochrane Library, Issue 2, 2007; MEDLINE; EMBASE; CINAHL and Science Citation Index were searched in June 2007. The Oxford Database of Perinatal Trials was searched in June 2004. Pediatric Research (abstracts of proceedings) were searched (1990 to April 2007) as were reference lists of identified trials and personal files. No language restrictions were applied.This search was updated in May 2011. Selection criteria for study inclusion were: randomised or quasi-randomised controlled trials in which intraventricular antibiotics with or without intravenous antibiotics were compared with intravenous antibiotics alone in neonates (< 28 days old) with meningitis. One of the following outcomes was required to be reported: mortality during initial hospitalisation; neonatal or infant mortality, or both; neurodevelopmental outcome; duration of hospitalisation; duration of culture positivity of CSF and side effects. All review authors abstracted information for outcomes reported and one review author checked for discrepancies and entered data into RevMan 5.1. Risk ratio (RR), risk difference (RD), number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH), and mean difference (MD), using the fixed-effect model are reported with 95% confidence intervals (CI

An antibiotic's journey from marketing authorization to use, Norway.

PubMed

Årdal, Christine; Blix, Hege Salvesen; Plahte, Jens; Røttingen, John-Arne

2017-03-01

Here we describe in detail marketing authorization and reimbursement procedures for medicinal products in Norway, with particular reference to nine novel antibiotics that received marketing authorization between 2005 and 2015. The description illustrates that, in places like Norway, with effective antibiotic stewardship policies and an associated low prevalence of antibiotic-resistant bacterial infection, there is little need for newer, more expensive antibiotics whose therapeutic superiority to existing compounds has not been demonstrated. Since resistance begins to emerge as soon as an antibiotic is used, Norway's practice of leaving newer antibiotics on the shelf is consistent with the goal of prolonging the effectiveness of newer antibiotics. An unintended consequence is that the country has signalled to the private sector that there is little commercial value in novel antibiotics, which may nevertheless still be needed to treat rare or emerging infections. Every country aims to improve infection control and to promote responsible antibiotic use. However, as progress is made, antibiotic-resistant bacteria should become less common and, consequently, the need for, and the commercial value of, novel antibiotics will probably be reduced. Nevertheless, antibiotic innovation continues to be essential. This dilemma will have to be resolved through the introduction of alternative reward systems for antibiotic innovation. The DRIVE-AB (Driving re-investment in research and development and responsible antibiotic use) research consortium in Europe has been tasked with identifying ways of meeting this challenge.

Variability in Antibiotic Use Across PICUs.

PubMed

Brogan, Thomas V; Thurm, Cary; Hersh, Adam L; Gerber, Jeffrey S; Smith, Michael J; Shah, Samir S; Courter, Joshua D; Patel, Sameer J; Parker, Sarah K; Kronman, Matthew P; Lee, Brian R; Newland, Jason G

2018-06-01

To characterize and compare antibiotic prescribing across PICUs to evaluate the degree of variability. Retrospective analysis from 2010 through 2014 of the Pediatric Health Information System. Forty-one freestanding children's hospital. Children aged 30 days to 18 years admitted to a PICU in children's hospitals contributing data to Pediatric Health Information System. To normalize for potential differences in disease severity and case mix across centers, a subanalysis was performed of children admitted with one of the 20 All Patient Refined-Diagnosis Related Groups and the seven All Patient Refined-Diagnosis Related Groups shared by all PICUs with the highest antibiotic use. The study included 3,101,201 hospital discharges from 41 institutions with 386,914 PICU patients. All antibiotic use declined during the study period. The median-adjusted antibiotic use among PICU patients was 1,043 days of therapy/1,000 patient-days (interquartile range, 977-1,147 days of therapy/1,000 patient-days) compared with 893 among non-ICU children (interquartile range, 805-968 days of therapy/1,000 patient-days). For PICU patients, the median adjusted use of broad-spectrum antibiotics was 176 days of therapy/1,000 patient-days (interquartile range, 152-217 days of therapy/1,000 patient-days) and was 302 days of therapy/1,000 patient-days (interquartile range, 220-351 days of therapy/1,000 patient-days) for antimethicillin-resistant Staphylococcus aureus agents, compared with 153 days of therapy/1,000 patient-days (interquartile range, 130-182 days of therapy/1,000 patient-days) and 244 days of therapy/1,000 patient-days (interquartile range, 203-270 days of therapy/1,000 patient-days) for non-ICU children. After adjusting for potential confounders, significant institutional variability existed in antibiotic use in PICU patients, in the 20 All Patient Refined-Diagnosis Related Groups with the highest antibiotic usage and in the seven All Patient Refined-Diagnosis Related Groups shared

21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals. 510.106 Section 510.106 Food and Drugs FOOD AND DRUG... ANIMAL DRUGS Specific Administrative Rulings and Decisions § 510.106 Labeling of antibiotic and...

Dispensing of non-prescribed antibiotics in Jordan

PubMed Central

Almaaytah, Ammar; Mukattash, Tareq L; Hajaj, Julia

2015-01-01

Objective Current regulations in Jordan state that antibiotics cannot be sold without a medical prescription. This study aimed to assess the percentage of pharmacies that dispense antibiotics without a medical prescription in the Kingdom of Jordan and identify and highlight the extent and seriousness of such practices among Jordanian pharmacies. Methods A prospective study was performed, and five different clinical scenarios were simulated at pharmacies investigated including sore throat, otitis media, acute sinusitis, diarrhea, and urinary tract infection in childbearing-aged women. Three levels of demand were used to convince the pharmacists to sell an antibiotic. Results A total of 202 total pharmacies in Jordan were visited in the present study. The majority of pharmacies (74.3%) dispensed antibiotics without prescription with three different levels of demand. The percentage of pharmacies dispensing antibiotics without a prescription for the sore throat scenario was 97.6%, followed by urinary tract infection (83.3%), diarrhea (83%), and otitis media (68.4%). The lowest percentage of antibiotic dispensing was for the acute sinusitis simulation at 48.5%. Among the pharmacies that dispensed antibiotics, the pharmacists provided an explanation as the number of times per day the drug should be taken in 95.3% of the cases, explained the duration of treatment in 25.7%, and inquired about allergies prior to the sale of the antibiotic in only 17.3%. Only 52 pharmacies (25.7%) refused to dispense any kind of antibiotics, the majority (61.5%) of this refusal response came from acute sinusitis cases, while the minority (2.4%) came from the sore throat cases. Conclusion The results of this study demonstrate that antibiotics continue to be dispensed without prescription in Jordan in violation with national regulations regarding this practice. The findings of this study could provide a layout for governmental health authorities to implement strict enfrorcment of national

Treating Wisely: The Surgeon's Role in Antibiotic Stewardship.

PubMed

Leeds, Ira L; Fabrizio, Anne; Cosgrove, Sara E; Wick, Elizabeth C

2017-05-01

: Antibiotic resistance continues to receive national attention as a leading public health threat. In 2015, President Barack Obama proposed a National Action Plan to Combat Antibiotic-Resistant Bacteria to curb the rise of "superbugs," bacteria resistant to antibiotics of last resort. Whereas many antibiotics are prescribed appropriately to treat infections, there continue to be a large number of inappropriately prescribed antibiotics. Although much of the national attention with regards to stewardship has focused on primary care providers, there is a significant opportunity for surgeons to embrace this national imperative and improve our practices. Local quality improvement efforts suggest that antibiotic misuse for surgical disease is common. Opportunities exist as part of day-to-day surgical care as well as through surgeons' interactions with nonsurgeon colleagues and policy experts. This article discusses the scope of the antibiotic misuse in surgery for surgical patients, and provides immediate practice improvements and also advocacy efforts surgeons can take to address the threat. We believe that surgical antibiotic prescribing patterns frequently do not adhere to evidence-based practices; surgeons are in a position to mitigate their ill effects; and antibiotic stewardship should be a part of every surgeons' practice.

[Antibiotic resistance : A challenge for society].

PubMed

Antão, Esther-Maria; Wagner-Ahlfs, Christian

2018-05-01

Without doubt, drug resistance is now one of the greatest health threats of our time. Not even 100 years after the discovery of the first antibiotics that saved human lives, we find ourselves threatened by the thought of a post-antibiotic era. Currently it is estimated that around 700,000 people die annually as a consequence of drug-resistant infections. Antibiotic resistance is a natural phenomenon with bacteria having devised several ways of combating the antibiotic attack. Rather than being a spontaneous event, resistance becomes an integral part of the microbe's genetic make-up, spreading further between and across species. However, the misuse and overuse of antibiotics over the years has in fact allowed for resistant bacteria to thrive, while slowly wiping out sensitive bacteria. Spreading awareness and proper information in the community about the risks and consequences of a rapidly developing antibiotic resistance is essential in tackling this global problem. In working together as an entire community, we can find long-lasting solutions. The One Health concept includes human and veterinary medical sectors, the environmental sector, as well as various decision-making bodies that include individual action as well as national and international policymakers. The role of stakeholders like pharmaceutical companies and agriculturists must be given importance, too, thinking all the while in a global context. Only this way will we find solutions for sustainable healthcare and together help slow down the process of antibiotic resistance.

Approach to osteomyelitis treatment with antibiotic loaded PMMA.

PubMed

Wentao, Zhang; Lei, Guangyu; Liu, Yang; Wang, Wei; Song, Tao; Fan, Jinzhu

2017-01-01

To reduce the incidence of osteomyelitis infection, local antibiotic impregnated delivery systems are commonly used as a promising and effective approach to deliver high antibiotic concentrations at the infection site. The objective of this review was to provide a literature review regarding approach to osteomyelitis treatment with antibiotic loaded PMMA. Literature study regarding osteomyelitis treatment with antibiotic loaded carriers using key terms Antibiotic, osteomyelitis, biodegradable PMMA through published articles. Hands searching of bibliographies of identified articles were also undertaken. We concluded that Antibiotic-impregnated PMMA beads are useful options for the treatment of osteomyelitis for prolonged drug therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of antibiotic restrictions: the ethical perspective.

PubMed

Garau, J

2006-08-01

Antibiotic restrictions present difficult choices for physicians, patients and payors. Physicians must choose between the welfare of the patient and the directive of healthcare systems to restrict antibiotics. These may be supported with incentives or penalties, causing a conflict of interest. The patient has an expectation of best care, but will often be unaware of antibiotic restriction policies and is therefore not fully informed about his/her treatment. For payors, reducing the volume of antibiotic prescribing and/or prescribing less expensive antibiotics are apparently attractive targets for cost savings. However, we are only now beginning to understand the downstream consequences of restricting antibiotics on outcomes and costs. We are hampered by the lack of a universal ethical framework and information on outcomes. In addition, the concept of 'effective' or 'best' therapy will vary among different groups. Balancing the risks of treating or not treating with antibiotics is complex. Suboptimal therapy, that fails to eradicate the bacterial infection, exposes the patient to the risk of poor outcome, adverse events and the wider risk of antimicrobial resistance. Failure to treat where the risk of a poor outcome exceeds the risk of an adverse event is also ethically unacceptable. The key to rational antibiotic prescribing is to identify those patients who need antibiotic therapy and optimise therapy to achieve the fastest bacterial and clinical cure. We are only now beginning to assemble the information and tools to be able to make such decisions. Above all, we should treat on the basis of knowledge.

Listeria monocytogenes: antibiotic resistance in food production.

PubMed

Lungu, Bwalya; O'Bryan, Corliss A; Muthaiyan, Arunachalam; Milillo, Sara R; Johnson, Michael G; Crandall, Philip G; Ricke, Steven C

2011-05-01

Listeria monocytogenes is an opportunistic human pathogen that causes listeriosis, a disease that mainly affects the immunocompromised, the elderly, infants, and pregnant women. Listeriosis has become increasingly common in the last 25 years since the first foodborne outbreak was noted. Treatment for listeriosis currently consists primarily of supportive therapy in conjunction with the use of intravenous antibiotics. Antibiotics have been commercially available for over 60 years for treatment of a myriad of clinical diseases. Bacteria resistant to antibiotics have been developing over this same period. This review seeks to elucidate the extent of antibiotic resistance in L. monocytogenes, the possible transmission mechanisms, and contributing factors to distribution of antibiotic resistance among Listeria species, and possible control strategies.

Antibiotic Resistance in Pediatric Urinary Tract Infections.

PubMed

Stultz, Jeremy S; Doern, Christopher D; Godbout, Emily

2016-12-01

Urinary tract infections (UTIs) are a common problem in pediatric patients. Resistance to common antibiotic agents appears to be increasing over time, although resistance rates may vary based on geographic region or country. Prior antibiotic exposure is a pertinent risk factor for acquiring resistant organisms during a first UTI and recurrent UTI. Judicious prescribing of antibiotics for common pediatric conditions is needed to prevent additional resistance from occurring. Complex pediatric patients with histories of hospitalizations, prior antibiotic exposure, and recurrent UTIs are also at high risk for acquiring UTIs due to extended spectrum beta-lactamase-producing organisms. Data regarding the impact of in vitro antibiotic susceptibility testing interpretation on UTI treatment outcomes is lacking.

Antibiotic resistance shaping multi-level population biology of bacteria

PubMed Central

Baquero, Fernando; Tedim, Ana P.; Coque, Teresa M.

2013-01-01

Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent “population biologies.” Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of “clinical” antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi

Antibiotic resistance shaping multi-level population biology of bacteria.

PubMed

Baquero, Fernando; Tedim, Ana P; Coque, Teresa M

2013-01-01

Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent "population biologies." Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of "clinical" antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi

Adsorption of antibiotics on microplastics.

PubMed

Li, Jia; Zhang, Kaina; Zhang, Hua

2018-06-01

Microplastics and antibiotics are two classes of emerging contaminants with proposed negative impacts to aqueous ecosystems. Adsorption of antibiotics on microplastics may result in their long-range transport and may cause compound combination effects. In this study, we investigated the adsorption of 5 antibiotics [sulfadiazine (SDZ), amoxicillin (AMX), tetracycline (TC), ciprofloxacin (CIP), and trimethoprim (TMP)] on 5 types of microplastics [polyethylene (PE), polystyrene (PS), polypropylene (PP), polyamide (PA), and polyvinyl chloride (PVC)] in the freshwater and seawater systems. Scanning Electron Microscope (SEM) and X-ray diffractometer (XRD) analysis revealed that microplastics have different surface characterizes and various degrees of crystalline. Adsorption isotherms demonstrated that PA had the strongest adsorption capacity for antibiotics with distribution coefficient (K d ) values ranged from 7.36 ± 0.257 to 756 ± 48.0 L kg -1 in the freshwater system, which can be attributed to its porous structure and hydrogen bonding. Relatively low adsorption capacity was observed on other four microplastics. The adsorption amounts of 5 antibiotics on PS, PE, PP, and PVC decreased in the order of CIP > AMX > TMP > SDZ > TC with K f correlated positively with octanol-water partition coefficients (Log K ow ). Comparing to freshwater system, adsorption capacity in seawater decreased significantly and no adsorption was observed for CIP and AMX. Our results indicated that commonly observed polyamide particles can serve as a carrier of antibiotics in the aquatic environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Antibiotics in the critically ill].

PubMed

Kolak, Radmila R

2010-01-01

Antibiotics are one the most common therapies administered in the intensive care unit setting. This review outlines the strategy for optimal use of antimicrobial agents in the critically ill. In severely ill patients, empirical antimicrobial therapy should be used when a suspected infection may impair the outcome. It is necessary to collect microbiological documentation before initiating empirical antimicrobial therapy. In addition to antimicrobial therapy, it is recommended to control a focus of infection and to modify factors that promote microbial growth or impair the host's antimicrobial defence. A judicious choice of antimicrobial therapy should be based on the host characteristics, the site of injection, the local ecology, and the pharmacokinetics/pharmacodynamics of antibiotics. This means treating empirically with broad-spectrum antimicrobials as soon as possible and narrowing the spectrum once the organism is identified (de-escalation), and limiting duration of therapy to the minimum effective period. Despite theoretical advantages, a combined antibiotic therapy is nor more effective than a mono-therapy in curing infections in most clinical trials involving intensive care patients. Nevertheless, textbooks and guidelines recommend a combination for specific pathogens and for infections commonly caused by these pathogens. Avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will improve patient outcomes while minimizing risks for the development of bacterial resistance. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilisation and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use be evaluated at the local level.

Antibiotics for preventing recurrent sore throat.

PubMed

Ng, Gareth J Y; Tan, Stephanie; Vu, Anh N; Del Mar, Chris B; van Driel, Mieke L

2015-07-14

Antibiotics are sometimes used to prevent recurrent sore throat, despite concern about resistance. However, there is conflicting primary evidence regarding their effectiveness. To assess the effects of antibiotics in patients with recurrent sore throat. The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 5); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 June 2015. Randomised controlled trials (RCTs) of antibiotics in adults and children suffering from pre-existing recurrent sore throat, defined as three or more sore throats in a year, examining the incidence of sore throat recurrence, with follow-up of at least 12 months post-antibiotic therapy. Two authors independently assessed trial quality and extracted data. Multiple attempts to contact the authors of one study yielded no response. We identified no trials that met the inclusion criteria for the review. We discarded the majority of the references retrieved from our search following screening of the title and abstract. We formally excluded four studies following review of the full-text report. There is insufficient evidence to determine the effectiveness of antibiotics for preventing recurrent sore throat. This finding must be balanced against the known adverse effects and cost of antibiotic therapy, when considering antibiotics for this purpose. There is a need for high quality RCTs that compare the effects of antibiotics versus placebo in adults and children with pre-existing recurrent sore throat on the following outcomes: incidence of sore throat recurrence, adverse effects, days off work and absence from school, and the incidence of complications. Future studies should be conducted and reported according to the CONSORT statement.

The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal

PubMed Central

Hu, Yongfei; Yang, Xi; Lu, Na; Zhu, Baoli

2014-01-01

Increasing evidence has accumulated to support that the human gut is a reservoir for antibiotic resistance genes. We previously identified more than 1000 genes displaying high similarity with known antibiotic resistance genes in the human gut gene set generated from the Chinese, Danish, and Spanish populations. Here, first, we add our new understanding of antibiotic resistance genes in the US and the Japanese populations; next, we describe the structure of a vancomycin-resistant operon in a Danish sample; and finally, we provide discussions on the correlation of the abundance of resistance genes in human gut with the antibiotic consumption in human medicine and in animal husbandry. These results, combined with those we published previously, provide comprehensive insights into the antibiotic resistance genes in the human gut microbiota at a population level. PMID:24637798

The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal.

PubMed

Hu, Yongfei; Yang, Xi; Lu, Na; Zhu, Baoli

2014-01-01

Increasing evidence has accumulated to support that the human gut is a reservoir for antibiotic resistance genes. We previously identified more than 1000 genes displaying high similarity with known antibiotic resistance genes in the human gut gene set generated from the Chinese, Danish, and Spanish populations. Here, first, we add our new understanding of antibiotic resistance genes in the US and the Japanese populations; next, we describe the structure of a vancomycin-resistant operon in a Danish sample; and finally, we provide discussions on the correlation of the abundance of resistance genes in human gut with the antibiotic consumption in human medicine and in animal husbandry. These results, combined with those we published previously, provide comprehensive insights into the antibiotic resistance genes in the human gut microbiota at a population level.

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

PubMed Central

Liu, Gang; Chandra, Govind; Niu, Guoqing

2013-01-01

SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor, the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes. PMID:23471619

Mechanisms of antibiotic resistance in Staphylococcus aureus.

PubMed

Pantosti, Annalisa; Sanchini, Andrea; Monaco, Monica

2007-06-01

Staphylococcus aureus can exemplify better than any other human pathogen the adaptive evolution of bacteria in the antibiotic era, as it has demonstrated a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin and methicillin, until the most recent, linezolid and daptomycin. Resistance mechanisms include enzymatic inactivation of the antibiotic (penicillinase and aminoglycoside-modification enzymes), alteration of the target with decreased affinity for the antibiotic (notable examples being penicillin-binding protein 2a of methicillin-resistant S. aureus and D-Ala-D-Lac of peptidoglycan precursors of vancomycin-resistant strains), trapping of the antibiotic (for vancomycin and possibly daptomycin) and efflux pumps (fluoroquinolones and tetracycline). Complex genetic arrays (staphylococcal chromosomal cassette mec elements or the vanA operon) have been acquired by S. aureus through horizontal gene transfer, while resistance to other antibiotics, including some of the most recent ones (e.g., fluoroquinolones, linezolid and daptomycin) have developed through spontaneous mutations and positive selection. Detection of the resistance mechanisms and their genetic basis is an important support to antibiotic susceptibility surveillance in S. aureus.

Biotherapeutics as alternatives to antibiotics

USDA-ARS?s Scientific Manuscript database

Increasing pressure to limit antibiotic use in agriculture is heightening the need for alternative methods to reduce the adverse effects of clinical and subclinical disease on livestock performance that are currently managed by in-feed antibiotic usage. Immunomodulators have long been sought as such...

Antibiotic use in livestock production

USDA-ARS?s Scientific Manuscript database

Antibiotic usage is a useful and commonly implemented practice in livestock and production agriculture that has progressively gained attention in recent years from consumers of animal products due to concerns about human and environmental health. Sub-therapeutic usage of antibiotics has led to a con...

Antibiotic resistance patterns of community-acquired urinary tract infections in children with vesicoureteral reflux receiving prophylactic antibiotic therapy.

PubMed

Cheng, Chi-Hui; Tsai, Ming-Horng; Huang, Yhu-Chering; Su, Lin-Hui; Tsau, Yong-Kwei; Lin, Chi-Jen; Chiu, Cheng-Hsun; Lin, Tzou-Yien

2008-12-01

The goal was to examine bacterial antimicrobial resistance of recurrent urinary tract infections in children receiving antibiotic prophylaxis because of primary vesicoureteral reflux. We reviewed data retrospectively for children with documented vesicoureteral reflux in 2 hospitals during a 5-year follow-up period. The patients were receiving co-trimoxazole, cephalexin, or cefaclor prophylaxis or prophylaxis with a sequence of different antibiotics (alternative monotherapy). Demographic data, degree of vesicoureteral reflux, prophylactic antibiotics prescribed, and antibiotic sensitivity results of first urinary tract infections and breakthrough urinary tract infections were recorded. Three hundred twenty-four patients underwent antibiotic prophylaxis (109 with co-trimoxazole, 100 with cephalexin, 44 with cefaclor, and 71 with alternative monotherapy) in one hospital and 96 children underwent co-trimoxazole prophylaxis in the other hospital. Breakthrough urinary tract infections occurred in patients from both hospitals (20.4% and 25%, respectively). Escherichia coli infection was significantly less common in children receiving antibiotic prophylaxis, compared with their initial episodes of urinary tract infection, at both hospitals. Children receiving cephalosporin prophylaxis were more likely to have an extended-spectrum beta-lactamase-producing organism for breakthrough urinary tract infections, compared with children with co-trimoxazole prophylaxis. Antimicrobial susceptibilities to almost all antibiotics decreased with cephalosporin prophylaxis when recurrent urinary tract infections developed. The extent of decreased susceptibilities was also severe for prophylaxis with a sequence of different antibiotics. However, antimicrobial susceptibilities decreased minimally in co-trimoxazole prophylaxis groups. Children receiving cephalosporin prophylaxis are more likely to have extended-spectrum beta-lactamase-producing bacteria or multidrug-resistant uropathogens

[New antibiotics - standstill or progress].

PubMed

Rademacher, J; Welte, T

2017-04-01

The development of resistance to antibiotics has been ignored for a long time. But nowadays, increasing resistance is an important topic. For a decade no new antibiotics had been developed and it is not possible to quickly close this gap of new resistance and no new drugs. This work presents six new antibiotics (ceftaroline, ceftobiprole, solithromycin, tedizolid, ceftolozane/tazobactam, ceftazidime/avibactam). In part, only expert opinions are given due to lack of study results.The two 5th generation cephalosporins ceftaroline and ceftobiprole have beside their equivalent efficacy to ceftriaxone (ceftaroline) and cefipim (ceftobiprole) high activity against MRSA. The fluoroketolide solithromycin should help against macrolide-resistant pathogens and has been shown to be noninferior to the fluorochinolones. The oxazolidinone tedizolid is effective against linezolid-resistant MRSA. The two cephalosporins ceftolozane/tazobactam and ceftazidime/avibactam are not only effective against gram-negative pathogens, but they have a very broad spectrum. Due to the efficacy against extended-spectrum β‑lactamases, they can relieve the selection pressure of the carbapenems. We benefit from all new antibiotics which can take the selection pressure from other often used antibiotics. The increasing number of resistant gram-negative pathogens worldwide is alarming. Thus, focusing on the development of new drugs is extremely important.

Antibiotic prescribing at the transition from hospitalization to discharge: a target for antibiotic stewardship

PubMed Central

Yogo, Norihiro; Haas, Michelle K; Knepper, Bryan C; Burman, William J; Mehler, Philip S; Jenkins, Timothy C

2016-01-01

Of 300 patients prescribed oral antibiotics at the time of hospital discharge, urinary tract infection, community-acquired pneumonia , and skin infections accounted for 181 (60%) of the treatment indications. Half of the prescriptions were antibiotics with broad gram-negative activity. Discharge prescriptions were inappropriate in 79 (53%) of 150 cases reviewed. PMID:25782905

The Impact of Maternal Antibiotics on Neonatal Disease.

PubMed

Reed, Benjamin D; Schibler, Kurt R; Deshmukh, Hitesh; Ambalavanan, Namasivayam; Morrow, Ardythe L

2018-06-01

We examined the impact of prenatal exposure to maternal antibiotics on risk of necrotizing enterocolitis (NEC), late onset sepsis (LOS), and death in infants born preterm. Secondary data analysis was conducted via an extant cohort of 580 infants born <32 weeks of gestation and enrolled in 3 level III neonatal intensive care units. Prenatal antibiotic exposure was defined as antibiotics received by the mother within 72 hours before delivery. Postnatal empiric antibiotic exposure was defined as antibiotic initiated within the first day of life without documented infection, categorized as low (<5 days) or high (>5 days) duration. Two-thirds of mothers received antibiotics within 72 hours before delivery, of whom 59.8% received >1 antibiotic. Ampicillin (37.6%) and azithromycin (26.4%) were the most common antibiotics given. NEC occurred in 7.5%, LOS in 11.1%, death in 9.6%, and the combined outcome of NEC, LOS, or death in 21.3% of study infants. In multiple logistic regression models adjusted for gestational age, postnatal empiric antibiotic exposure, and other factors, prenatal antibiotic exposure was associated with reduced risk of NEC (OR 0.28; 95% CI 0.14-0.56; P < .001), death (OR 0.29; 95% CI 0.14-0.60; P = .001), but not LOS (OR 1.59; 95% CI 0.84-2.99; P = .15), although protection was significant for the combined outcome (OR 0.52, P < .001). High postnatal empiric antibiotic exposure was associated with greater risk of death but not other outcomes in multiple regression models (OR 3.18, P = .002). Prenatal antibiotic exposure was associated with lower rates of NEC or death of infants born preterm, and its impact on infant outcomes warrants further study. Copyright © 2018 Elsevier Inc. All rights reserved.

Antibiotics impact plant traits, even at small concentrations

PubMed Central

Deloy, Andrea; Volkert, Anna Martina; Leonhardt, Sara Diana; Pufal, Gesine

2017-01-01

Abstract Antibiotics of veterinary origin are released to agricultural fields via grazing animals or manure. Possible effects on human health through the consumption of antibiotic exposed crop plants have been intensively investigated. However, information is still lacking on the effects of antibiotics on plants themselves, particularly on non-crop species, although evidence suggests adverse effects of antibiotics on growth and performance of plants. This study evaluated the effects of three major antibiotics, penicillin, sulfadiazine and tetracycline, on the germination rates and post-germinative traits of four plant species during ontogenesis and at the time of full development. Antibiotic concentrations were chosen as to reflect in vivo situations, i.e. concentrations similar to those detected in soils. Plant species included two herb species and two grass species, and represent two crop-species and two non-crop species commonly found in field margins, respectively. Germination tests were performed in climate chambers and effects on the remaining plant traits were determined in greenhouse experiments. Results show that antibiotics, even in small concentrations, significantly affect plant traits. These effects include delayed germination and post-germinative development. Effects were species and functional group dependent, with herbs being more sensitive to antibiotics then grasses. Responses were either negative or positive, depending on plant species and antibiotic. Effects were generally stronger for penicillin and sulfadiazine than for tetracycline. Our study shows that cropland species respond to the use of different antibiotics in livestock industry, for example, with delayed germination and lower biomass allocation, indicating possible effects on yield in farmland fertilized with manure containing antibiotics. Also, antibiotics can alter the composition of plant species in natural field margins, due to different species-specific responses, with unknown

Adjunctive use of antibiotics in periodontal therapy

PubMed Central

Barca, Ece; Cifcibasi, Emine; Cintan, Serdar

2015-01-01

Periodontal diseases are infectious diseases with a mixed microbial aetiology and marked inflammatory response leading to destruction of underlying tissue. Periodontal therapy aims to eliminate pathogens associated with the disease and attain periodontal health. Periodontitis is generally treated by nonsurgical mechanical debridement and regular periodontal maintenance care. Periodontal surgery may be indicated for some patients to improve access to the root surface; however, mechanical debridement alone may not be helpful in all cases. In such cases, adjunctive systemic antibiotic therapy remains the treatment of choice. It can reach microorganisms at the base of the deep periodontal pockets and furcation areas via serum, and also affects organisms residing within gingival epithelium and connective tissue. This review aims to provide an update on clinical issues regarding when and how to prescribe systemic antibiotics in periodontal therapy. The points discussed are the mode of antibiotic action, susceptible periodontal pathogens, antibiotic dosage, antibiotic use in treatment of periodontal disease, and mechanism of bacterial resistance to each antibiotic. PMID:28955547

The environmental release and fate of antibiotics.

PubMed

Manzetti, Sergio; Ghisi, Rossella

2014-02-15

Antibiotics have been used as medical remedies for over 50 years and have recently emerged as new pollutants in the environment. This review encompasses the fate of several antibiotics in the environment, including sulfonamides, nitrofurans, terfenadines, cephalosporins and cyclosporins. It investigates the cycle of transfer from humans and animals including their metabolic transformation. The results show that antibiotic metabolites are of considerable persistence and are localized to ground-water and drinking water supplies. Furthermore, the results also show that several phases of the cycle of antibiotics in the environment are not well understood, such as how low concentrations of antibiotic metabolites in the diet affect humans and animals. This review also shows that improved wastewater decontamination processes are remediating factors for these emerging pollutants. The results obtained here may help legislators and authorities in understanding the fate and transformation of antibiotics in the environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

[New antibiotics produced by Bacillus subtilis strains].

PubMed

Malanicheva, I A; Kozlov, D G; Efimenko, T A; Zenkova, V A; Kastrukha, G S; Reznikova, M I; Korolev, A M; Borshchevskaia, L N; Tarasova, O D; Sineokiĭ, S P; Efremenkova, O V

2014-01-01

Two Bacillus subtilis strains isolated from the fruiting body of a basidiomycete fungus Pholiota squarrosa exhibited a broad range of antibacterial activity, including those against methicillin-resistant Staphylococcus aureus INA 00761 (MRSA) and Leuconostoc mes6nteroides VKPM B-4177 resistant to glycopep-> tide antibiotics, as well as antifungal activity. The strains were identified as belonging to the "B. subtilis" com- plex based on their morphological and physiological characteristics, as well as by sequencing of the 16S rRNA gene fragments. Both strains (INA 01085 and INA 01086) produced insignificant amounts of polyene antibiotics (hexaen and pentaen, respectively). Strain INA 01086 produced also a cyclic polypeptide antibiotic containing Asp, Gly, Leu, Pro, Tyr, Thr, Trp, and Phe, while the antibiotic of strain INA 01085 contained, apart from these, two unidentified nonproteinaceous amino acids. Both polypeptide antibiotics were new compounds efficient against gram-positive bacteria and able to override the natural bacterial antibiotic resistance.

Bacterial uptake of antibiotics in model unsaturated systems

NASA Astrophysics Data System (ADS)

Zhang, W.; Chen, Z.; Zhang, Y.; Zhao, Z.; Wang, G.; Gao, Y.; Boyd, S. A.; Zhu, D.; Li, H.

2016-12-01

Anthropogenic antibiotics are ubiquitously present in the environment due to large uses in human medicine and animal agriculture, and are causing unintended consequence to human and ecosystem health. Bacterial uptake of antibiotics could exert selection pressure on antibiotic resistance development among bacteria population. Therefore, understanding environmental factors controlling bioavailability of antibiotics to bacteria is critical to better assessing exposure risks and developing mitigation strategies. Nonetheless, conventional bioavailability assays are often performed in water-saturated systems that do not represent unsaturated soils where most bacteria live, therefore neglecting soil water as a controlling factor in determining the extent of antibiotic bacterial uptake. Therefore, we propose to study bacterial uptake of antibiotics in model unsaturated systems using GFP-tagged Escherichia coli bioreporter for tetracyclines. Our preliminary studies demonstrated the important role of water content (or water matric potential) in determining the bioavailability of antibiotics, and complex interactions of water potential, tetracycline diffusion, and E. coli growth. Therefore, unsaturated processes are important for understanding antibiotic resistance development and developing mitigation strategies.

An evolutionary model to predict the frequency of antibiotic resistance under seasonal antibiotic use, and an application to Streptococcus pneumoniae

PubMed Central

Lehtinen, Sonja; Fraser, Christophe

2017-01-01

The frequency of resistance to antibiotics in Streptococcus pneumoniae has been stable over recent decades. For example, penicillin non-susceptibility in Europe has fluctuated between 12% and 16% without any major time trend. In spite of long-term stability, resistance fluctuates over short time scales, presumably in part due to seasonal fluctuations in antibiotic prescriptions. Here, we develop a model that describes the evolution of antibiotic resistance under selection by multiple antibiotics prescribed at seasonally changing rates. This model was inspired by, and fitted to, published data on monthly antibiotics prescriptions and frequency of resistance in two communities in Israel over 5 years. Seasonal fluctuations in antibiotic usage translate into small fluctuations of the frequency of resistance around the average value. We describe these dynamics using a perturbation approach that encapsulates all ecological and evolutionary forces into a generic model, whose parameters quantify a force stabilizing the frequency of resistance around the equilibrium and the sensitivity of the population to antibiotic selection. Fitting the model to the data revealed a strong stabilizing force, typically two to five times stronger than direct selection due to antibiotics. The strong stabilizing force explains that resistance fluctuates in phase with usage, as antibiotic selection alone would result in resistance fluctuating behind usage with a lag of three months when antibiotic use is seasonal. While most antibiotics selected for increased resistance, intriguingly, cephalosporins selected for decreased resistance to penicillins and macrolides, an effect consistent in the two communities. One extra monthly prescription of cephalosporins per 1000 children decreased the frequency of penicillin-resistant strains by 1.7%. This model emerges under minimal assumptions, quantifies the forces acting on resistance and explains up to 43% of the temporal variation in resistance. PMID

Increased Antibiotic Release from a Bone Cement Containing Bacterial Cellulose

PubMed Central

Nakai, Takahisa; Enomoto, Koichi; Uchio, Yuji; Yoshino, Katsumi

2010-01-01

Background Major disadvantages of antibiotic bone cements include limited drug release and reduced strength resulting from the addition of high doses of antibiotics. Bacterial cellulose, a three-dimensional hydrophilic mesh, may retain antibiotics and release them gradually. We hypothesized that the addition of cellulose to antibiotic bone cement would improve mechanical strength and antibiotic release. Questions/purposes We therefore examined the mechanical strength and antibiotic release of cellulose antibiotic cement. Methods A high dose of antibiotics (5 g per 40 g cement powder) was incorporated into bacterial cellulose and then mixed with bone cement. We compared the compression strength, fracture toughness, fatigue life, and elution kinetics of this formulation with those of plain cement and a traditional antibiotic cement. Results The average values for compression strength, fracture toughness, and fatigue life of the cellulose antibiotic cement were 97%, 97%, and 78% of the values obtained for plain cement, respectively. The corresponding values for the traditional antibiotic cement were 79%, 82%, and 17%, respectively. The cumulative elution over 35 days was 129% greater from the cellulose antibiotic cement than from the traditional antibiotic cement. Conclusions With a high dose of antibiotics, incorporating cellulose into the bone cement prevented compression and fracture fragility, improved fatigue life, and increased antibiotic elution. Clinical Relevance Antibiotic cements containing cellulose may have applications in clinical situations that require high levels of antibiotic release and preservation of the mechanical properties of the cement. PMID:20945120

Antibiotic use and resistance in animals: Belgian initiatives.

PubMed

Daeseleire, Els; De Graef, Evelyne; Rasschaert, Geertrui; De Mulder, Thijs; Van den Meersche, Tina; Van Coillie, Els; Dewulf, Jeroen; Heyndrickx, Marc

2016-05-01

The widespread use of antibiotics in animals is causing concerns about the growing risk for development and the spread of antibiotic-resistant bacteria. Antibiotic consumption is higher in animals than in humans as reported in a joint publication of EFSA (European Food Safety Agency), ECDC (European Centre for Disease Prevention and Control), and EMA (European Medicines Agency) using data from 2011 and 2012. Both in humans and animals, positive associations between the consumption of antibiotics and resistant bacteria are observed. Responsible use of antibiotics in humans and animals should therefore be promoted. In this paper some general aspects of antibiotic resistance such as microbiological versus clinical resistance, intrinsic versus acquired resistance, resistance mechanisms, and transfer of resistance are briefly introduced. In 2012, the Belgian Center of Expertise on Antimicrobial Consumption and Resistance in Animals (AMCRA) was founded. Its mission is to collect and analyze all data related to antibiotic use and resistance in animals in Belgium and to communicate these findings in a neutral and objective manner. One of AMCRA's 10 objectives is a 50% reduction in antibiotic consumption in veterinary medicine in Belgium by 2020. The aim of this paper is to report on the achievements of this national project. The Institute for Agricultural and Fisheries Research (ILVO, Merelbeke-Melle), in collaboration with Ghent University, is currently working on three nationally funded projects on antibiotic resistance in animal husbandry. In the first project, an in vitro model is used to study the influence of low antibiotic concentrations due to carry-over after production and usage of medicated feed on the development of resistance in the pig gut. Part of that project is to develop a quantitative risk assessment model. A second project focuses on tracking excreted antibiotics used in pig rearing and their influence on the development of antibiotic resistance in pig

Every antibiotic, every day: Maximizing the impact of prospective audit and feedback on total antibiotic use

PubMed Central

Decloe, Melissa; Gill, Suzanne; Ho, Grace; McCready, Janine; Powis, Jeff

2017-01-01

Background The success of antimicrobial stewardship is dependent on how often it is completed and which antimicrobials are targeted. We evaluated the impact of an antimicrobial stewardship program (ASP) in three non-ICU settings where all systemic antibiotics, regardless of spectrum, were targeted on the first weekday after initiation. Methods Prospective audit and feedback (PAAF) was initiated on the surgical, respiratory, and medical wards of a community hospital on July 1, 2010, October 1, 2010, and April 1, 2012, respectively. We evaluated rates of total antibiotic use, measured in days on therapy (DOTs), among all patients admitted to the wards before and after PAAF initiation using an interrupted time series analysis. Changes in antibiotic costs, rates of C. difficile infection (CDI), mortality, readmission, and length of stay were evaluated using univariate analyses. Results Time series modelling demonstrated that total antibiotic use decreased (± standard error) by 100 ± 51 DOTs/1,000 patient-days on the surgical wards (p = 0.049), 100 ± 46 DOTs/1,000 patient-days on the respiratory ward (p = 0.029), and 91 ± 33 DOTs/1,000 patient-days on the medical wards (p = 0.006) immediately following PAAF initiation. Reductions in antibiotic use were sustained up to 50 months after intervention initiation, and were accompanied by decreases in antibiotic costs. There were no significant changes to patient outcomes on the surgical and respiratory wards following intervention initiation. On the medical wards, however, readmission increased from 4.6 to 5.6 per 1,000 patient-days (p = 0.043), while mortality decreased from 7.4 to 5.0 per 1,000 patient-days (p = 0.001). CDI rates showed a non-significant declining trend after PAAF initiation. Conclusions ASPs can lead to cost-effective, sustained reductions in total antibiotic use when interventions are conducted early in the course of therapy and target all antibiotics. Shifting to such a model may help strengthen the

Every antibiotic, every day: Maximizing the impact of prospective audit and feedback on total antibiotic use.

PubMed

Campbell, Tonya J; Decloe, Melissa; Gill, Suzanne; Ho, Grace; McCready, Janine; Powis, Jeff

2017-01-01

The success of antimicrobial stewardship is dependent on how often it is completed and which antimicrobials are targeted. We evaluated the impact of an antimicrobial stewardship program (ASP) in three non-ICU settings where all systemic antibiotics, regardless of spectrum, were targeted on the first weekday after initiation. Prospective audit and feedback (PAAF) was initiated on the surgical, respiratory, and medical wards of a community hospital on July 1, 2010, October 1, 2010, and April 1, 2012, respectively. We evaluated rates of total antibiotic use, measured in days on therapy (DOTs), among all patients admitted to the wards before and after PAAF initiation using an interrupted time series analysis. Changes in antibiotic costs, rates of C. difficile infection (CDI), mortality, readmission, and length of stay were evaluated using univariate analyses. Time series modelling demonstrated that total antibiotic use decreased (± standard error) by 100 ± 51 DOTs/1,000 patient-days on the surgical wards (p = 0.049), 100 ± 46 DOTs/1,000 patient-days on the respiratory ward (p = 0.029), and 91 ± 33 DOTs/1,000 patient-days on the medical wards (p = 0.006) immediately following PAAF initiation. Reductions in antibiotic use were sustained up to 50 months after intervention initiation, and were accompanied by decreases in antibiotic costs. There were no significant changes to patient outcomes on the surgical and respiratory wards following intervention initiation. On the medical wards, however, readmission increased from 4.6 to 5.6 per 1,000 patient-days (p = 0.043), while mortality decreased from 7.4 to 5.0 per 1,000 patient-days (p = 0.001). CDI rates showed a non-significant declining trend after PAAF initiation. ASPs can lead to cost-effective, sustained reductions in total antibiotic use when interventions are conducted early in the course of therapy and target all antibiotics. Shifting to such a model may help strengthen the effectiveness of ASPs in non

Variability in antibiotic use across Ontario acute care hospitals.

PubMed

Tan, Charlie; Vermeulen, Marian; Wang, Xuesong; Zvonar, Rosemary; Garber, Gary; Daneman, Nick

2017-02-01

Antibiotic stewardship is a required organizational practice for Canadian acute care hospitals, yet data are scarce regarding the quantity and composition of antibiotic use across facilities. We sought to examine the variability, and risk-adjusted variability, in antibiotic use across acute care hospitals in Ontario, Canada's most populous province. Antibiotic purchasing data from IMS Health, previously demonstrated to correlate strongly with internal antibiotic dispensing data, were acquired for 129 Ontario hospitals from January to December 2014 and linked to patient day (PD) denominator data from administrative datasets. Hospital variation in DDDs/1000 PDs was determined for overall antibiotic use, class-specific use and six practices of clinical or ecological significance. Multivariable risk adjustment for hospital and patient characteristics was used to compare observed versus expected utilization. There was 7.4-fold variability in the quantity of antibiotic use across the 129 acute care hospitals, from 253 to 1873 DDDs/1000 PDs. Variation was evident within hospital subtypes, exceeded that explained by hospital and patient characteristics, and included wide variability in proportion of broad-spectrum antibiotics (IQR 36%-48%), proportion of fluoroquinolones among respiratory antibiotics (IQR 40%-62%), proportion of ciprofloxacin among urinary anti-infectives (IQR 44%-60%), proportion of antibiotics with highest risk for Clostridium difficile (IQR 29%-40%), proportion of 'reserved-use' antibiotics (IQR 0.8%-3.5%) and proportion of anti-pseudomonal antibiotics among antibiotics with Gram-negative coverage (IQR 26%-40%). There is extensive variability in antibiotic use, and risk-adjusted use, across acute care hospitals. This could motivate, focus and benchmark antibiotic stewardship efforts. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email

Select antibiotics in leachate from closed and active landfills exceed thresholds for antibiotic resistance development.

PubMed

Chung, S S; Zheng, J S; Burket, S R; Brooks, B W

2018-06-01

Though antibiotic resistance (ABR) represents a major global health threat, contributions of landfill leachate to the life cycle of antibiotics and ABR development are poorly understood in rapidly urbanizing regions of developing countries. We selected one of the largest active landfills in Asia and two landfills that have been closed for 20 years to examine antibiotic occurrences in leachates and associated hazards during wet and dry season sampling events. We focused on some of the most commonly used human antibiotics in Hong Kong, one of the most populous Asian cities and the fourth most densely populated cities in the world. Seven antibiotics (cephalexin [CLX], chloramphenicol [CAP], ciprofloxacin [CIP], erythromycin [ERY], roxithromycin [ROX], trimethoprim [TMP], sulfamethoxazole [SMX]) were quantitated using HPLC-MS/MS generally following previously reported methods. Whereas CLX, CAP, ROX and SMX in leachates did not exceed ABR predicted no effect concentrations (PNECs), exceedances were observed for CIP, ERY and TMP in some study locations and on some dates. In fact, an ABR PNEC for CIP was exceeded in leachates during both sampling periods from all study locations, including leachates that are directly discharged to coastal systems. These findings highlight the importance of developing an advanced understanding of pharmaceutical access, usage and disposal practices, effectiveness of intervention strategies (e.g., leachate treatment technologies, drug take-back schemes), and contributions of landfill leachates to the life cycle of antibiotics and ABR development, particularly in rapidly urbanizing coastal regions with less advanced waste management systems than Hong Kong. Copyright © 2018 Elsevier Ltd. All rights reserved.

Duration of antibiotic therapy in the intensive care unit.

PubMed

Zilahi, Gabor; McMahon, Mary Aisling; Povoa, Pedro; Martin-Loeches, Ignacio

2016-12-01

There are certain well defined clinical situations where prolonged therapy is beneficial, but prolonged duration of antibiotic therapy is associated with increased resistance, medicalising effects, high costs and adverse drug reactions. The best way to decrease antibiotic duration is both to stop antibiotics when not needed (sterile invasive cultures with clinical improvement), not to start antibiotics when not indicated (treating colonization) and keep the antibiotic course as short as possible. The optimal duration of antimicrobial treatment for ventilator-associated pneumonia (VAP) is unknown, however, there is a growing evidence that reduction in the length of antibiotic courses to 7-8 days can minimize the consequences of antibiotic overuse in critical care, including antibiotic resistance, adverse effects, collateral damage and costs. Biomarkers like C-reactive protein (CRP) and procalcitonin (PCT) do have a valuable role in helping guide antibiotic duration but should be interpreted cautiously in the context of the clinical situation. On the other hand, microbiological criteria alone are not reliable and should not be used to justify a prolonged antibiotic course, as clinical cure does not equate to microbiological eradication. We do not recommend a 'one size fits all' approach and in some clinical situations, including infection with non-fermenting Gram-negative bacilli (NF-GNB) clinical evaluation is needed but shortening the antibiotic course is an effective and safe way to decrease inappropriate antibiotic exposure.

Antibiotic Rotation for Febrile Neutropenic Patients with Hematological Malignancies: Clinical Significance of Antibiotic Heterogeneity

PubMed Central

Chong, Yong; Shimoda, Shinji; Yakushiji, Hiroko; Ito, Yoshikiyo; Miyamoto, Toshihiro; Kamimura, Tomohiko; Shimono, Nobuyuki; Akashi, Koichi

2013-01-01

Background Our unit adopted the single administration of cefepime as the initial treatment for febrile episodes in neutropenic patients with hematological malignancies. However, recently, cefepime-resistant gram-negative bacteremia, including those with extended-spectrum β-lactamase (ESBL)-producers, was frequently observed in these patients. Therefore, we instituted a rotation of primary antibiotics for febrile neutropenic patients in an attempt to control antibiotic resistance. Methods This prospective trial was performed from August 2008 through March 2011 at our unit. After a pre-intervention period, in which cefepime was used as the initial agent for febrile neutropenia, 4 primary antibiotics, namely, piperacillin-tazobactam, ciprofloxacin, meropenem, and cefepime, were rotated at 1-month intervals over 20 months. Blood and surveillance cultures were conducted for febrile episodes, in order to assess the etiology, the resistance pattern (particularly to cefepime), and the prognosis. Results In this trial, 219 patients were registered. A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P<0.01). Interestingly, ESBL-related bacteremia was not detected after the initiation of the trial (1.7 vs 0.0 episodes per 1000 patient days before and after intervention respectively, P<0.01). Infection-related mortality was comparable between the 2 periods. Conclusions We implemented a monthly rotation of primary antibiotics for febrile neutropenic patients. An antibiotic heterogeneity strategy, mainly performed as a cycling regimen, would be useful for controlling antimicrobial resistance among patients treated for febrile neutropenia. PMID:23372683

Antibiotic Therapy of Staphylococcal Infections

PubMed Central

Hawks, Gordon H.

1965-01-01

The antibiotic treatment of staphylococcal infections remains a problem. Isolation of the organism and sensitivity testing are necessary in the choice of antibiotic. Penicillin G is the most effective penicillin against non-penicillinase-producing staphy-lococci; for the penicillinase producers there is very little to choose between the semisynthetic penicillins, methicillin, cloxacillin, nafcillin and oxacillin. For patients who are hypersensitive to penicillin, the bacteriostatic drugs (erythromycin, novobiocin, tetracycline, chloramphenicol, oleandomycin) are useful for mild infections, while for more severe illness the bactericidal drugs (vancomycin, ristocetin, kanamycin, bacitracin, neomycin) have been used successfully. Acute staphylococcal enterocolitis is probably best treated by a semisynthetic penicillin. Other antibiotics which have been found useful, with clinical trials, for staphylococcal infections are cephalosporin, fucidin, cephaloridine and lincomycin. The latter drug has been reported of value in the treatment of osteomyelitis. There is little justification for the prophylactic use of antibiotics to prevent staphylococcal infection. Surgical drainage is still an important adjunct in the treatment of many staphylococcal infections. PMID:5318575

Use of antibiotics in paediatric long-term care facilities.

PubMed

Murray, M T; Johnson, C L; Cohen, B; Jackson, O; Jones, L K; Saiman, L; Larson, E L; Neu, N

2018-06-01

Adult long-term care (LTC) facilities have high rates of antibiotic use, raising concerns about antimicrobial resistance. Few studies have examined antibiotic use in paediatric LTC facilities. To describe antibiotic use in three paediatric LTC facilities and to describe the factors associated with use. A retrospective cohort study was conducted from September 2012 to December 2015 in three paediatric LTC facilities. Medical records were reviewed for demographics, healthcare-associated infections (HAIs), antimicrobial use and diagnostic testing. Logistic regression was used to identify predictors for antibiotic use. The association between susceptibility testing results and appropriate antibiotic coverage was determined using Chi-squared test. Fifty-eight percent (413/717) of residents had at least one HAI, and 79% (325/413) of these residents were treated with at least one antibiotic course, totalling 2.75 antibiotic courses per 1000 resident-days. Length of enrolment greater than one year, having a neurological disorder, having a tracheostomy, and being hospitalized at least once during the study period were significantly associated with receiving antibiotics when controlling for facility (all P < 0.001). Diagnostic testing was performed for 40% of antibiotic-treated HAIs. Eighty-six percent of antibiotic courses for identified bacterial pathogens (201/233) provided appropriate coverage. Access to susceptibility testing was not associated with appropriate antibiotic choice (P = 0.26). Use of antibiotics in paediatric LTC facilities is widespread. There is further need to assess antibiotic use in paediatric LTC facilities. Evaluation of the adverse outcomes associated with inappropriate antibiotic use, including the prevalence of resistant organisms in paediatric LTC facilities, is critical. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Inactivation of an integrated antibiotic resistance gene in mammalian cells to re-enable antibiotic selection.

PubMed

Ni, Peiling; Zhang, Qian; Chen, Haixia; Chen, Lingyi

2014-01-01

Removing an antibiotic resistance gene allows the same antibiotic to be re-used in the next round of genetic manipulation. Here we applied the CRISPR/Cas system to disrupt the puromycin resistance gene in an engineered mouse embryonic stem cell line and then re-used puromycin selection in the resulting cells to establish stable reporter cell lines. With the CRISPR/Cas system, pre-engineered sequences, such as loxP or FRT, are not required. Thus, this technique can be used to disrupt antibiotic resistance genes that cannot be removed by the Cre-loxP and Flp-FRT systems.

Nudging Guideline-Concordant Antibiotic Prescribing

PubMed Central

Meeker, Daniella; Knight, Tara K.; Friedberg, Mark W.; Linder, Jeffrey A.; Goldstein, Noah J.; Fox, Craig R.; Rothfeld, Alan; Diaz, Guillermo; Doctor, Jason N.

2015-01-01

IMPORTANCE “Nudges” that influence decision making through subtle cognitive mechanisms have been shown to be highly effective in a wide range of applications, but there have been few experiments to improve clinical practice. OBJECTIVE To investigate the use of a behavioral “nudge” based on the principle of public commitment in encouraging the judicious use of antibiotics for acute respiratory infections (ARIs). DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial in 5 outpatient primary care clinics. A total of 954 adults had ARI visits during the study timeframe: 449 patients were treated by clinicians randomized to the posted commitment letter (335 in the baseline period, 114 in the intervention period); 505 patients were treated by clinicians randomized to standard practice control (384 baseline, 121 intervention). INTERVENTIONS The intervention consisted of displaying poster-sized commitment letters in examination rooms for 12 weeks. These letters, featuring clinician photographs and signatures, stated their commitment to avoid inappropriate antibiotic prescribing for ARIs. MAIN OUTCOMES AND MEASURES Antibiotic prescribing rates for antibiotic-inappropriate ARI diagnoses in baseline and intervention periods, adjusted for patient age, sex, and insurance status. RESULTS Baseline rates were 43.5% and 42.8% for control and poster, respectively. During the intervention period, inappropriate prescribing rates increased to 52.7% for controls but decreased to 33.7% in the posted commitment letter condition. Controlling for baseline prescribing rates, we found that the posted commitment letter resulted in a 19.7 absolute percentage reduction in inappropriate antibiotic prescribing rate relative to control (P = .02). There was no evidence of diagnostic coding shift, and rates of appropriate antibiotic prescriptions did not diminish over time. CONCLUSIONS AND RELEVANCE Displaying poster-sized commitment letters in examination rooms decreased inappropriate

[Antibiotic-resistant bacteria and new directions of antimicrobial chemotherapy].

PubMed

Tateda, Kazuhiro

2012-05-01

The emergence and spread of antibiotic-resistant organisms are becoming more and more serious and are a worldwide problem. Recent trends in new antibiotic-resistant organisms include multiple-drug resistant Pseudomonas aeruginosa (MDRP), MDR-Acinetobacter baumannii (MDR-AB) and New Deli metallo beta-lactamase-1 (NDM-1) -producing bacteria. Antibiotic combination therapy is an option to overcome these MDR organisms. A breakpoint checkerboard plate was created to measure antibiotic combination effects at breakpoint concentrations, making it possible to evaluate the synergy of antibiotic combination within 24 hours. In this article, recent topics regarding antibiotic-resistant organisms are briefly reviewed and the directions of antibiotic chemotherapy against these organisms are discussed.

Emergence and dissemination of antibiotic resistance: a global problem.

PubMed

Choudhury, R; Panda, S; Singh, D V

2012-01-01

Antibiotic resistance is a major problem in clinical health settings. Interestingly the origin of many of antibiotic resistance mechanisms can be traced back to non-pathogenic environmental organisms. Important factors leading to the emergence and spread of antibiotic resistance include absence of regulation in the use of antibiotics, improper waste disposal and associated transmission of antibiotic resistance genes in the community through commensals. In this review, we discussed the impact of globalisation on the transmission of antibiotic resistance genes in bacteria through immigration and export/import of foodstuff. The significance of surveillance to define appropriate use of antibiotics in the clinic has been included as an important preventive measure.

Isolated cell behavior drives the evolution of antibiotic resistance

PubMed Central

Artemova, Tatiana; Gerardin, Ylaine; Dudley, Carmel; Vega, Nicole M; Gore, Jeff

2015-01-01

Bacterial antibiotic resistance is typically quantified by the minimum inhibitory concentration (MIC), which is defined as the minimal concentration of antibiotic that inhibits bacterial growth starting from a standard cell density. However, when antibiotic resistance is mediated by degradation, the collective inactivation of antibiotic by the bacterial population can cause the measured MIC to depend strongly on the initial cell density. In cases where this inoculum effect is strong, the relationship between MIC and bacterial fitness in the antibiotic is not well defined. Here, we demonstrate that the resistance of a single, isolated cell—which we call the single-cell MIC (scMIC)—provides a superior metric for quantifying antibiotic resistance. Unlike the MIC, we find that the scMIC predicts the direction of selection and also specifies the antibiotic concentration at which selection begins to favor new mutants. Understanding the cooperative nature of bacterial growth in antibiotics is therefore essential in predicting the evolution of antibiotic resistance. PMID:26227664

Antibiotics as immunomodulant agents in COPD.

PubMed

Blasi, Francesco; Mantero, Marco; Aliberti, Stefano

2012-06-01

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. Copyright © 2012 Elsevier Ltd. All rights reserved.

Prescription of antibiotics and awareness of antibiotic costs by paediatricians in two hospitals in Greece.

PubMed

Maltezou, Helena C; Mougkou, Katerina; Iosifidis, Elias; Katerelos, Panos; Roilides, Emmanuel; Theodoridou, Maria

2014-02-01

Our aim was to study the antibiotic prescription practices and the knowledge about antibiotic costs, brand and generic drugs of paediatricians working in two hospitals in Greece. The 2007 national guidelines were used as the gold standard for antibiotic prescription. A total of 126 paediatricians participated in the study (50.4% response rate). The mean compliance rate with the guidelines was 50.1% (range per infection: 10.6-84.7%). The mean scores of knowledge about antibiotic costs and about brand name and generic drugs were 35.6 and 60.3%, respectively. Linear regression analysis found a significant association between the mean compliance rate with the national guidelines and the paediatricians' age (mean compliance rates were 49.1, 53.0, and 43.0% in the ≤ 30, 31-40, and > 40 years age-groups, respectively; P  =  0.003). In conclusion, five years after the first national guidelines were issued in Greece only half of the paediatricians working in hospitals comply fully with them.

Hybrid antibiotics - clinical progress and novel designs.

PubMed

Parkes, Alastair L; Yule, Ian A

2016-07-01

There is a growing need for new antibacterial agents, but success in development of antibiotics in recent years has been limited. This has led researchers to investigate novel approaches to finding compounds that are effective against multi-drug resistant bacteria, and that delay onset of resistance. One such strategy has been to link antibiotics to produce hybrids designed to overcome resistance mechanisms. The concept of dual-acting hybrid antibiotics was introduced and reviewed in this journal in 2010. In the present review the authors sought to discover how clinical candidates described had progressed, and to examine how the field has developed. In three sections the authors cover the clinical progress of hybrid antibiotics, novel agents produced from hybridisation of two or more small-molecule antibiotics, and novel agents produced from hybridisation of antibiotics with small-molecules that have complementary activity. Many key questions regarding dual-acting hybrid antibiotics remain to be answered, and the proposed benefits of this approach are yet to be demonstrated. While Cadazolid in particular continues to progress in the clinic, suggesting that there is promise in hybridisation through covalent linkage, it may be that properties other than antibacterial activity are key when choosing a partner molecule.

Alternatives to antibiotics-a pipeline portfolio review.

PubMed

Czaplewski, Lloyd; Bax, Richard; Clokie, Martha; Dawson, Mike; Fairhead, Heather; Fischetti, Vincent A; Foster, Simon; Gilmore, Brendan F; Hancock, Robert E W; Harper, David; Henderson, Ian R; Hilpert, Kai; Jones, Brian V; Kadioglu, Aras; Knowles, David; Ólafsdóttir, Sigríður; Payne, David; Projan, Steve; Shaunak, Sunil; Silverman, Jared; Thomas, Christopher M; Trust, Trevor J; Warn, Peter; Rex, John H

2016-02-01

Antibiotics have saved countless lives and enabled the development of modern medicine over the past 70 years. However, it is clear that the success of antibiotics might only have been temporary and we now expect a long-term and perhaps never-ending challenge to find new therapies to combat antibiotic-resistant bacteria. A broader approach to address bacterial infection is needed. In this Review, we discuss alternatives to antibiotics, which we defined as non-compound approaches (products other than classic antibacterial agents) that target bacteria or any approaches that target the host. The most advanced approaches are antibodies, probiotics, and vaccines in phase 2 and phase 3 trials. This first wave of alternatives to antibiotics will probably best serve as adjunctive or preventive therapies, which suggests that conventional antibiotics are still needed. Funding of more than £1·5 billion is needed over 10 years to test and develop these alternatives to antibiotics. Investment needs to be partnered with translational expertise and targeted to support the validation of these approaches in phase 2 trials, which would be a catalyst for active engagement and investment by the pharmaceutical and biotechnology industry. Only a sustained, concerted, and coordinated international effort will provide the solutions needed for the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tet and sul antibiotic resistance genes in livestock lagoons of various operation type, configuration, and antibiotic occurrence

USGS Publications Warehouse

McKinney, C.W.; Loftin, K.A.; Meyer, M.T.; Davis, J.G.; Pruden, A.

2010-01-01

Although livestock operations are known to harbor elevated levels of antibiotic resistant bacteria, few studies have examined the potential of livestock waste lagoons to reduce antibiotic resistance genes (ARGs). The purpose of this study was to determine the prevalence and examine the behavior of tetracycline [tet(O) and tet(W)] and sulfonamide [sul(I) and su/(II)] ARGsin a broad cross-section of livestock lagoons within the same semiarid western watershed. ARGs were monitored for one year in the water and the settled solids of eight lagoon systems by quantitative polymerase chain reaction. In addition, antibiotic residues and various bulk water quality constituents were analyzed. It was found that the lagoons of the chicken layer operation had the lowest concentrations of both tet and sul ARGs and low total antibiotic concentrations, whereas su ARGs were highest in the swine lagoons, which generally corresponded to the highest total antibiotic concentrations. A marginal benefit of organic and small dairy operations also was observed compared to conventional and large dairies, respectively. In all lagoons, su ARGs were observed to be generally more recalcitrant than tet ARGs. Also, positive correlations of various bulk water quality constituents were identified with tet ARGs but not sul ARGs. Significant positive correlations were identified between several metals and tet ARGs, but Pearson's correlation coefficients were mostly lower than those determined between antibiotic residues and ARGs. This study represents a quantitative characterization of ARGs in lagoons across a variety of livestock operations and provides insight into potential options for managing antibiotic resistance emanating from agricultural activities. ?? 2010 American Chemical Society.

Bacterial Cheating Limits the Evolution of Antibiotic Resistance

NASA Astrophysics Data System (ADS)

Yurtsev, Eugene; Xiao Chao, Hui; Datta, Manoshi; Artemova, Tatiana; Gore, Jeff

2012-02-01

The emergence of antibiotic resistance in bacteria is a significant health concern. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removal of the antibiotic. The presence of a cooperative mechanism of resistance suggests that a cheater strain - which does not contribute to breaking down the antibiotic - may be able to take advantage of resistant cells. We find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We use a simple model in conjunction with difference equations to explain the observed population dynamics as a function of cell density and antibiotic concentration. Our experimental difference equations resemble the logistic map, raising the possibility of oscillations or even chaotic dynamics.

Antibiotic Sensitivity of Micrococcus radiodurans

PubMed Central

Hawiger, J.; Jeljaszewicz, J.

1967-01-01

A wild-type strain of Micrococcus radiodurans and its nonpigmented mutant W1 were tested for sensitivity to 10 antibiotics selected from the standpoint of their mechanism of action. Representatives of groups of antibiotics inhibiting deoxyribonucleic acid (DNA) synthesis, DNA-dependent ribonucleic acid synthesis, protein synthesis, and cell wall synthesis were selected. M. radiodurans and its mutant exhibited full susceptibility to all antibiotics tested (mitomycin C, actinomycin D, chloramphenicol, dihydrostreptomycin, erythromycin, neomycin, kanamycin, benzylpenicillin, bacitracin, and vancomycin), the degree of susceptibility being of the same order as that of a standard strain of Staphylococcus aureus 209 P, with the exception of dihydrostreptomycin. PMID:4166078

Lysobacter species: a potential source of novel antibiotics.

PubMed

Panthee, Suresh; Hamamoto, Hiroshi; Paudel, Atmika; Sekimizu, Kazuhisa

2016-11-01

Infectious diseases threaten global health due to the ability of microbes to acquire resistance against clinically used antibiotics. Continuous discovery of antibiotics with a novel mode of action is thus required. Actinomycetes and fungi are currently the major sources of antibiotics, but the decreasing rate of discovery of novel antibiotics suggests that the focus should be changed to previously untapped groups of microbes. Lysobacter species have a genome size of ~6 Mb with a relatively high G + C content of 61-70 % and are characterized by their ability to produce peptides that damage the cell walls or membranes of other microbes. Genome sequence analysis revealed that each Lysobacter species has gene clusters for the production of 12-16 secondary metabolites, most of which are peptides, thus making them 'peptide production specialists'. Given that the number of antibiotics isolated is much lower than the number of gene clusters harbored, further intensive studies of Lysobacter are likely to unearth novel antibiotics with profound biomedical applications. In this review, we summarize the structural diversity, activity and biosynthesis of lysobacterial antibiotics and highlight the importance of Lysobacter species for antibiotic production.

A Tick Antivirulence Protein Potentiates Antibiotics against Staphylococcus aureus

PubMed Central

Abraham, Nabil M.; Liu, Lei; Jutras, Brandon L.; Murfin, Kristen; Acar, Ali; Yarovinsky, Timur O.; Sutton, Erica; Heisig, Martin; Jacobs-Wagner, Christine

2017-01-01

ABSTRACT New strategies are needed to combat antibiotic resistance, especially against pathogens such as methicillin-resistant Staphylococcus aureus. A tick antifreeze glycoprotein, IAFGP, possesses potent antibiofilm properties against a variety of clinical pathogens, including S. aureus. Synergy between IAFGP, or a peptide (P1) representative of a repeat region of the protein, with different antibiotics was assessed in vitro. Antibiotics that synergized with either IAFPG or P1 were further evaluated in vivo using vertebrate and invertebrate infection models. IAFGP readily enhanced the efficacy of antibiotics against S. aureus. Synergy with daptomycin, an antibiotic used to treat methicillin-resistant S. aureus, was observed in vitro and in vivo using iafgp-transgenic mice and flies. Furthermore, synergy with ciprofloxacin or gentamicin, antibiotics not generally used to treat S. aureus, was also perceived. The combined effect of the antibiotic and IAFGP was associated with improved permeation of the antibiotic into the cell. Our results highlight that synergy of IAFGP with antibiotics traditionally used to treat this pathogen, and enhancement of the potency of antibiotics not commonly used against this microbe, can provide novel alternative therapeutic strategies to combat bacterial infections. PMID:28438938

The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial.

PubMed

van Duijn, Pleun Joppe; Verbrugghe, Walter; Jorens, Philippe Germaine; Spöhr, Fabian; Schedler, Dirk; Deja, Maria; Rothbart, Andreas; Annane, Djillali; Lawrence, Christine; Nguyen Van, Jean-Claude; Misset, Benoit; Jereb, Matjaz; Seme, Katja; Šifrer, Franc; Tomiç, Viktorija; Estevez, Francisco; Carneiro, Jandira; Harbarth, Stephan; Eijkemans, Marinus Johannes Cornelis; Bonten, Marc

2018-04-01

Whether antibiotic rotation strategies reduce prevalence of antibiotic-resistant, Gram-negative bacteria in intensive care units (ICUs) has not been accurately established. We aimed to assess whether cycling of antibiotics compared with a mixing strategy (changing antibiotic to an alternative class for each consecutive patient) would reduce the prevalence of antibiotic-resistant, Gram-negative bacteria in European intensive care units (ICUs). In a cluster-randomised crossover study, we randomly assigned ICUs to use one of three antibiotic groups (third-generation or fourth-generation cephalosporins, piperacillin-tazobactam, and carbapenems) as preferred empirical treatment during 6-week periods (cycling) or to change preference after every consecutively treated patient (mixing). Computer-based randomisation of intervention and rotated antibiotic sequence was done centrally. Cycling or mixing was applied for 9 months; then, following a washout period, the alternative strategy was implemented. We defined antibiotic-resistant, Gram-negative bacteria as Enterobacteriaceae with extended-spectrum β-lactamase production or piperacillin-tazobactam resistance, and Acinetobacter spp and Pseudomonas aeruginosa with piperacillin-tazobactam or carbapenem resistance. Data were collected for all admissions during the study. The primary endpoint was average, unit-wide, monthly point prevalence of antibiotic-resistant, Gram-negative bacteria in respiratory and perineal swabs with adjustment for potential confounders. This trial is registered with ClinicalTrials.gov, number NCT01293071. Eight ICUs (from Belgium, France, Germany, Portugal, and Slovenia) were randomly assigned and patients enrolled from June 27, 2011, to Feb 16, 2014. 4069 patients were admitted during the cycling periods in total and 4707 were admitted during the mixing periods. Of these, 745 patients during cycling and 853 patients during mixing were present during the monthly point-prevalence surveys, and were

Resistance diagnosis and the changing epidemiology of antibiotic resistance.

PubMed

McAdams, David

2017-01-01

Widespread adoption of point-of-care resistance diagnostics (POCRD) reduces ineffective antibiotic use but could increase overall antibiotic use. Indeed, in the context of a standard susceptible-infected epidemiological model with a single antibiotic, POCRD accelerates the rise of resistance in the disease-causing bacterial population. When multiple antibiotics are available, however, POCRD may slow the rise of resistance even as more patients receive antibiotic treatment, belying the conventional wisdom that antibiotics are "exhaustible resources" whose increased use necessarily promotes the rise of resistance. © 2017 New York Academy of Sciences.

Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection

NASA Astrophysics Data System (ADS)

Surawicz, Christina M.

Diarrhea is a common side effect of antibiotics. Antibiotics can cause diarrhea in 5-25% of individuals who take them but its occurrence is unpredictable. Diarrhea due to antibiotics is called antibiotic-associated diarrhea (AAD). Diarrhea may be mild and resolve when antibiotics are discontinued, or it may be more severe. The most severe form of AAD is caused by overgrowth of Clostridium difficile which can cause severe diarrhea, colitis, pseudomembranous colitis, or even fatal toxic megacolon. Rates of diarrhea vary with the specific antibiotic as well as with the individual susceptibility.

Antibiotic administration in the drinking water of mice.

PubMed

Marx, James O; Vudathala, Daljit; Murphy, Lisa; Rankin, Shelley; Hankenson, F Claire

2014-05-01

Although antibiotics frequently are added to the drinking water of mice, this practice has not been tested to confirm that antibiotics reach therapeutic concentrations in the plasma of treated mice. In the current investigation, we 1) tested the stability of enrofloxacin and doxycycline in the drinking water of adult, female C57BL/6 mice; 2) measured the mice's consumption of water treated with enrofloxacin, doxycycline, amoxicillin, or trimethoprim-sulfamethoxazole; and 3) used HPLC to measure plasma antibiotic concentrations in mice that had ingested treated water for 1 wk. Plasma concentrations of antibiotic were measured 1 h after the start of both the light and dark cycle. The main findings of the study were that both enrofloxacin and nonpharmaceutical, chemical-grade doxycycline remained relatively stable in water for 1 wk. In addition, mice consumed similar volumes of antibiotic-treated and untreated water. The highest plasma antibiotic concentrations measured were: enrofloxacin, 140.1 ± 10.4 ng/mL; doxycycline, 56.6 ± 12.5 ng/mL; amoxicillin, 299.2 ± 64.1 ng/mL; and trimethoprim-sulfamethoxazole, 5.9 ± 1.2 ng/mL. Despite the stability of the antibiotics in the water and predictable water consumption by mice, the plasma antibiotic concentrations were well below the concentrations required for efficacy against bacterial pathogens, except for those pathogens that are exquisitely sensitive to the antibiotic. The findings of this investigation prompt questions regarding the rationale of the contemporary practice of adding antibiotics to the drinking water of mice for systemic antibacterial treatments.

Antibiotic Administration in the Drinking Water of Mice

PubMed Central

Marx, James O; Vudathala, Daljit; Murphy, Lisa; Rankin, Shelley; Hankenson, F Claire

2014-01-01

Although antibiotics frequently are added to the drinking water of mice, this practice has not been tested to confirm that antibiotics reach therapeutic concentrations in the plasma of treated mice. In the current investigation, we 1) tested the stability of enrofloxacin and doxycycline in the drinking water of adult, female C57BL/6 mice; 2) measured the mice's consumption of water treated with enrofloxacin, doxycycline, amoxicillin, or trimethoprim–sulfamethoxazole; and 3) used HPLC to measure plasma antibiotic concentrations in mice that had ingested treated water for 1 wk. Plasma concentrations of antibiotic were measured 1 h after the start of both the light and dark cycle. The main findings of the study were that both enrofloxacin and nonpharmaceutical, chemical-grade doxycycline remained relatively stable in water for 1 wk. In addition, mice consumed similar volumes of antibiotic-treated and untreated water. The highest plasma antibiotic concentrations measured were: enrofloxacin, 140.1 ± 10.4 ng/mL; doxycycline, 56.6 ± 12.5 ng/mL; amoxicillin, 299.2 ± 64.1 ng/mL; and trimethoprim–sulfamethoxazole, 5.9 ± 1.2 ng/mL. Despite the stability of the antibiotics in the water and predictable water consumption by mice, the plasma antibiotic concentrations were well below the concentrations required for efficacy against bacterial pathogens, except for those pathogens that are exquisitely sensitive to the antibiotic. The findings of this investigation prompt questions regarding the rationale of the contemporary practice of adding antibiotics to the drinking water of mice for systemic antibacterial treatments. PMID:24827573

Should Aerosolized Antibiotics Be Used to Treat Ventilator-Associated Pneumonia?

PubMed

Zhang, Changsheng; Berra, Lorenzo; Klompas, Michael

2016-06-01

In patients with ventilator-associated pneumonia, systemic use of antibiotics is the cornerstone of medical management. Supplemental use of aerosolized antibiotics with intravenous antibiotics in both experimental and clinical studies has been shown to have the following pharmacologic benefits: (1) aerosolized antibiotics reach the infected lung parenchyma without crossing the pulmonary alveolar capillary barrier; (2) aerosolized antibiotics increase anti-bacterial efficacy through increased local antibiotic concentration; and (3) aerosolized antibiotics decrease systemic toxicity. These benefits may be particularly beneficial to treat pneumonia caused by multidrug-resistant pathogens. Clinical data on the benefits of aerosolized antibiotics are more limited. Studies to date have not clearly shown improvements in time to extubation, mortality, or other patient-centered outcomes. At present, amikacin, colistin, and ceftazidime are the most frequently used and studied aerosolized antibiotics. This review summarizes the characteristics of aerosolized antibiotics, reviews the advantages and disadvantages of using aerosolized antibiotics, and calls for future investigations based on animal study data. Copyright © 2016 by Daedalus Enterprises.

Clostridium difficile infection: update on emerging antibiotic treatment options and antibiotic resistance

PubMed Central

Shah, Dhara; Dang, Minh-Duc; Hasbun, Rodrigo; Koo, Hoonmo L; Jiang, Zhi-Dong; DuPont, Herbert L; Garey, Kevin W

2010-01-01

Clostridium difficile infection (CDI) is the most common cause of identifiable diarrhea in hospitalized patients. The incidence and severity of CDIs are increasing. The increased incidence and severity of the disease has sparked interest in the optimal treatment of CDI as well as the use of new therapies and drug discovery. Current treatment strategies are inadequate with decreased response rates to metronidazole, and high recurrence rates with the use of metronidazole and oral vancomycin. Although incidence rates continue to be low, in vitro resistance to antibiotics used for the treatment of CDI has been noted. Recently, important data has emerged on new anti-C. difficile antibiotics such as rifaximin, rifalazil, fidaxomicin, nitazoxanide, tigecycline and ramoplanin. The purpose of this review is to provide an update on the in vitro susceptibility and new antibiotic treatment options for CDI. This review will focus primarily on scientific studies published in the last 36 months in order to provide an up-to-date review on the topic. PMID:20455684

Biomarker-guided antibiotic therapy—strengths and limitations

PubMed Central

Salluh, Jorge; Martin-Loeches, Ignacio; Póvoa, Pedro

2017-01-01

Biomarkers as C-reactive protein (CRP) and procalcitonin (PCT) emerged as tools to help clinicians to diagnose infection and to properly initiate and define the duration of antibiotic therapy. Several randomized controlled trials, including adult critically ill patients, showed that PCT-guided antibiotic stewardship was repeatedly associated with a decrease in the duration of antibiotic therapy with no apparent harm. There are however some relevant limitations in these trials namely the low rate of compliance of PCT-guided algorithms, the high rate of exclusion (without including common clinical situations and pathogens) and the long duration of antibiotic therapy in control groups. Such limitations weakened the real impact of such algorithms in the clinical decision-making process and strengthened the concept that the initiation and the duration of antibiotic therapy cannot depend solely on a biomarker. Future efforts should address these limitations in order to better clarify the role of biomarkers on the complex and multifactorial issue of antibiotic management and to deeply understand its potential effect on mortality. PMID:28603723

Biomarker-guided antibiotic therapy-strengths and limitations.

PubMed

Nora, David; Salluh, Jorge; Martin-Loeches, Ignacio; Póvoa, Pedro

2017-05-01

Biomarkers as C-reactive protein (CRP) and procalcitonin (PCT) emerged as tools to help clinicians to diagnose infection and to properly initiate and define the duration of antibiotic therapy. Several randomized controlled trials, including adult critically ill patients, showed that PCT-guided antibiotic stewardship was repeatedly associated with a decrease in the duration of antibiotic therapy with no apparent harm. There are however some relevant limitations in these trials namely the low rate of compliance of PCT-guided algorithms, the high rate of exclusion (without including common clinical situations and pathogens) and the long duration of antibiotic therapy in control groups. Such limitations weakened the real impact of such algorithms in the clinical decision-making process and strengthened the concept that the initiation and the duration of antibiotic therapy cannot depend solely on a biomarker. Future efforts should address these limitations in order to better clarify the role of biomarkers on the complex and multifactorial issue of antibiotic management and to deeply understand its potential effect on mortality.

Bacterial Adaptation to Antibiotics through Regulatory RNAs.

PubMed

Felden, Brice; Cattoir, Vincent

2018-05-01

The extensive use of antibiotics has resulted in a situation where multidrug-resistant pathogens have become a severe menace to human health worldwide. A deeper understanding of the principles used by pathogens to adapt to, respond to, and resist antibiotics would pave the road to the discovery of drugs with novel mechanisms. For bacteria, antibiotics represent clinically relevant stresses that induce protective responses. The recent implication of regulatory RNAs (small RNAs [sRNAs]) in antibiotic response and resistance in several bacterial pathogens suggests that they should be considered innovative drug targets. This minireview discusses sRNA-mediated mechanisms exploited by bacterial pathogens to fight against antibiotics. A critical discussion of the newest findings in the field is provided, with emphasis on the implication of sRNAs in major mechanisms leading to antibiotic resistance, including drug uptake, active drug efflux, drug target modifications, biofilms, cell walls, and lipopolysaccharide (LPS) biosynthesis. Of interest is the lack of knowledge about sRNAs implicated in Gram-positive compared to Gram-negative bacterial resistance. Copyright © 2018 American Society for Microbiology.

[Antibiotic diffusion to central nervous system].

PubMed

Cabrera-Maqueda, J M; Fuentes Rumí, L; Valero López, G; Baidez Guerrero, A E; García Molina, E; Díaz Pérez, J; García-Vázquez, E

2018-02-01

Central nervous system (CNS) infections caused by pathogens with a reduced sensitivity to drugs are a therapeutic challenge. Transport of fluid and solutes is tightly controlled within CNS, where vasculature exhibits a blood-brain barrier (BBB).The entry of drugs, including antibiotics, into the cerebro-spinal fluid (CSF) is governed by molecular size, lipophilicity, plasma protein binding and their affinity to transport systems at the BBB. The ratio of the AUCCSF (Area under the curve in CSF)/AUCS (Area under the curve in serum) is the most accurate parameter to characterize drug penetration into the CSF. Linezolid, some fluoroquinolones and metronidazole get high CSF concentrations and are useful for treating susceptible pathogens. Some highly active antibiotic compounds with low BBB permeability can be directly administered into the ventricles together with concomitant intravenous therapy. The ideal antibiotic to treat CNS infections should be that with a small moderately lipophilic molecule, low plasma protein binding and low affinity to efflux pumps at BBB. Knowledge of the pharmacokinetics and pharmacodynamics of antibiotics at the BBB will assist to optimize antibiotic treatment in CNS infections. This article reviews the physicochemical properties of the main groups of antibiotics to assess which compounds are most promising for the treatment of CNS infections and how to use them in the daily clinical practice. © The Author 2018. Published by Sociedad Española de Quimioterapia.

Nano-antibiotics in chronic lung infection therapy against Pseudomonas aeruginosa.

PubMed

Hadinoto, Kunn; Cheow, Wean Sin

2014-04-01

Antibiotic encapsulation into nanoparticle carriers has emerged as a promising inhaled antibiotic formulation for treatment of chronic Pseudomonas aeruginosa lung infection prevalent in chronic obstructive pulmonary diseases. Attributed to their prolonged lung retention, sustained antibiotic release, and mucus penetrating ability, antibiotic nanoparticles, or nano-antibiotics in short, can address the principal weakness of inhaled antibiotic solution, i.e. low antibiotic exposure in the vicinity of P. aeruginosa biofilm colonies resulting in diminished anti-pseudomonal efficacy after repeated uses. This review details the current state of development and limitations of the two most widely studied forms of nano-antibiotics, i.e. liposomes and polymer nanoparticles. Factors in their formulation that influence the anti-pseudomonal efficacy in vitro and in vivo, such as liposome's membrane rigidity, surface charge, size, and polymer hydrophobicity, are discussed. This review reveals that the superior anti-pseudomonal efficacy of liposomal antibiotics to free antibiotics has been clearly established when they are correctly formulated, with several liposomal antibiotic formulations are currently undergoing clinical trials. Liposomal antibiotics, nevertheless, are not without limitation due to their weak physicochemical stability. In contrast, only mucus penetrating ability of the more stable polymeric nano-antibiotics has been established, while their anti-pseudomonal efficacy has only been examined in vitro from which their superiority to free antibiotics has not been ascertained. Lastly, future research needs to bring liposome and polymer-based nano-antibiotics closer to their clinical realization are identified. Copyright © 2014 Elsevier B.V. All rights reserved.

Bacteriocins - exploring alternatives to antibiotics in mastitis treatment.

PubMed

Pieterse, Reneé; Todorov, Svetoslav D

2010-07-01

Mastitis is considered to be the most costly disease affecting the dairy industry. Management strategies involve the extensive use of antibiotics to treat and prevent this disease. Prophylactic dosages of antibiotics used in mastitis control programmes could select for strains with resistance to antibiotics. In addition, a strong drive towards reducing antibiotic residues in animal food products has lead to research in finding alternative antimicrobial agents. In this review we have focus on the pathogenesis of the mastitis in dairy cows, existing antibiotic treatments and possible alternative for application of bacteriocins from lactic acid bacteria in the treatment and prevention of this disease.

Antibiotics for acute otitis media in children.

PubMed

Venekamp, Roderick P; Sanders, Sharon; Glasziou, Paul P; Del Mar, Chris B; Rovers, Maroeska M

2013-01-31

Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Antibiotic use for AOM varies from 56% in the Netherlands to 95% in the USA, Canada and Australia. To assess the effects of antibiotics for children with AOM. We searched CENTRAL (2012, Issue 10), MEDLINE (1966 to October week 4, 2012), OLDMEDLINE (1958 to 1965), EMBASE (January 1990 to November 2012), Current Contents (1966 to November 2012), CINAHL (2008 to November 2012) and LILACS (2008 to November 2012). Randomised controlled trials (RCTs) comparing 1) antimicrobial drugs with placebo and 2) immediate antibiotic treatment with expectant observation (including delayed antibiotic prescribing) in children with AOM. Two review authors independently assessed trial quality and extracted data. For the review of antibiotics against placebo, 12 RCTs (3317 children and 3854 AOM episodes) from high-income countries were eligible. However, one trial did not report patient-relevant outcomes, leaving 11 trials with generally low risk of bias. Pain was not reduced by antibiotics at 24 hours (risk ratio (RR) 0.89; 95% confidence interval (CI) 0.78 to 1.01) but almost a third fewer had residual pain at two to three days (RR 0.70; 95% CI 0.57 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) 20) and fewer had pain at four to seven days (RR 0.79; 95% CI 0.66 to 0.95; NNTB 20). When compared with placebo, antibiotics did not alter the number of abnormal tympanometry findings at either four to six weeks (RR 0.92; 95% CI 0.83 to 1.01) or at three months (RR 0.97; 95% CI 0.76 to 1.24), or the number of AOM recurrences (RR 0.93; 95% CI 0.78 to 1.10). However, antibiotic treatment did lead to a statistically significant reduction of tympanic membrane perforations (RR 0.37; 95% CI 0.18 to 0.76; NNTB 33) and halved contralateral AOM episodes (RR 0.49; 95% CI 0.25 to 0.95; NNTB 11) as compared with placebo. Severe complications were rare and did not differ between

Inhaled Antibiotics for Lower Airway Infections

PubMed Central

Quon, Bradley S.; Goss, Christopher H.

2014-01-01

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post–lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized “off-label” to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated. PMID:24673698

Inhaled antibiotics for lower airway infections.

PubMed

Quon, Bradley S; Goss, Christopher H; Ramsey, Bonnie W

2014-03-01

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

Overcoming the current deadlock in antibiotic research.

PubMed

Schäberle, Till F; Hack, Ingrid M

2014-04-01

Antibiotic-resistant bacteria are on the rise, making it harder to treat bacterial infections. The situation is aggravated by the shrinking of the antibiotic development pipeline. To finance urgently needed incentives for antibiotic research, creative financing solutions are needed. Public-private partnerships (PPPs) are a successful model for moving forward. Copyright © 2013 Elsevier Ltd. All rights reserved.

Removal of five fluoroquinolone antibiotics during broiler manure composting.

PubMed

Yang, Bing; Meng, Lei; Xue, Nandong

2018-02-01

Composting is a cost-effective approach for the removal of antibiotics from the environment; however, the consequence of this approach on fluoroquinolone antibiotics is limited. The fate of five representative fluoroquinolone antibiotics, namely ciprofloxacin, enrofloxacin, lomefloxacin, norfloxacin, and sarafloxacin, was investigated in a pilot-scale composting of broiler manure over 42 days. The effect of antibiotic concentrations (at a dose of 15, 30, or 60 mg/kg for each and a control without antibiotic addition) on the composting process was also assessed. The 42-day composting showed 45.3-75.4% of antibiotic removal with species-specific patterns. However, the observed variations in such removal among both antibiotics concentrations and composting times were not significant in most cases, possibly indicating a slight side-effect of the tested antibiotic concentrations on the composting process. To the best of our knowledge, this study is among few studies with a focus on the persistence of fluoroquinolone antibiotics during a pilot-scale composting, which warrants further study in regards to the mechanism underlying the removal of these compounds during composting.

The role of healthcare strategies in controlling antibiotic resistance.

PubMed

Aziz, Ann-Marie

In an interview in March 2013, the Chief Medical Officer described antibiotic resistance as a 'ticking time bomb' and ranked it along with terrorism on a list of threats to the nation. Her report Infections and the Rise of Antimicrobial Resistance (Department of Health, 2011) highlighted that, while a new infectious disease has been discovered nearly every year over the past three decades, there have been very few new antibiotics developed, leaving our armoury nearly empty. Antibiotic resistance is a universal problem that needs to be tackled by a wide variety of strategies and players. Our approach to tackling resistance to antibiotic agents must therefore also be dynamic. As well as reducing environmental use, we also need to lower antibiotic use in the healthcare setting. Healthcare workers have a huge role to play in combating antibiotic resistance. This article focuses on several issues related to antibiotic resistance, including antibiotic modes of action and the properties that confer resistance on bacteria. It includes information on antibiotic usage and describes current healthcare strategies we can adopt to help reduce the development of resistance.

A New Approach for the Discovery of Antibiotics by Targeting Non-Multiplying Bacteria: A Novel Topical Antibiotic for Staphylococcal Infections

PubMed Central

Hu, Yanmin; Shamaei-Tousi, Alireza; Liu, Yingjun; Coates, Anthony

2010-01-01

In a clinical infection, multiplying and non-multiplying bacteria co-exist. Antibiotics kill multiplying bacteria, but they are very inefficient at killing non-multipliers which leads to slow or partial death of the total target population of microbes in an infected tissue. This prolongs the duration of therapy, increases the emergence of resistance and so contributes to the short life span of antibiotics after they reach the market. Targeting non-multiplying bacteria from the onset of an antibiotic development program is a new concept. This paper describes the proof of principle for this concept, which has resulted in the development of the first antibiotic using this approach. The antibiotic, called HT61, is a small quinolone-derived compound with a molecular mass of about 400 Daltons, and is active against non-multiplying bacteria, including methicillin sensitive and resistant, as well as Panton-Valentine leukocidin-carrying Staphylococcus aureus. It also kills mupirocin resistant MRSA. The mechanism of action of the drug is depolarisation of the cell membrane and destruction of the cell wall. The speed of kill is within two hours. In comparison to the conventional antibiotics, HT61 kills non-multiplying cells more effectively, 6 logs versus less than one log for major marketed antibiotics. HT61 kills methicillin sensitive and resistant S. aureus in the murine skin bacterial colonization and infection models. No resistant phenotype was produced during 50 serial cultures over a one year period. The antibiotic caused no adverse affects after application to the skin of minipigs. Targeting non-multiplying bacteria using this method should be able to yield many new classes of antibiotic. These antibiotics may be able to reduce the rate of emergence of resistance, shorten the duration of therapy, and reduce relapse rates. PMID:20676403

Antibiotic resistance genes in surface water of eutrophic urban lakes are related to heavy metals, antibiotics, lake morphology and anthropic impact.

PubMed

Yang, Yuyi; Xu, Chen; Cao, Xinhua; Lin, Hui; Wang, Jun

2017-08-01

Urban lakes are impacted by heavy human activities and represent potential reservoirs for antibiotic resistance genes. In this study, six urban lakes in Wuhan, central China were selected to analyze the distribution of sulfonamide resistance (sul) genes, tetracycline resistance (tet) genes and quinolone resistance (qnr) genes and their relationship with heavy metals, antibiotics, lake morphology and anthropic impact. sul1 and sul2 were detected in all six lakes and dominated the types of antibiotic resistance genes, which accounted for 86.28-97.79% of the total antibiotic resistance gene abundance. For eight tested tet genes, antibiotic efflux pumps (tetA, tetB, tetC, and tetG) genes were all observed in six lakes and had higher relative abundance than ribosomal protection protein genes (tetM and tetQ). For 4 plasmid mediated quinolone resistance genes, only qnrD is found in all six lakes. The class I integron (intI1) is also found to be a very important media for antibiotic resistance gene propagation in urban lakes. The results of redundancy analysis and variation partitioning analysis showed that antibiotic and co-selection with heavy metals were the major factors driving the propagation of antibiotic resistance genes in six urban lakes. The heavily eutrophic Nanhu Lake and Shahu Lake which located in a high density building area with heavy human activities had the higher relative abundance of total antibiotic resistance genes. Our study could provide a useful reference for antibiotic resistance gene abundance in urban lakes with high anthropic impact.

Community perceptions of infectious diseases, antibiotic use and antibiotic resistance in context of environmental changes: a study in Odisha, India

PubMed Central

Sahoo, Krushna Chandra; Tamhankar, Ashok J.; Johansson, Eva; Stålsby Lundborg, Cecilia

2012-01-01

Abstract Background  The public health impact of environmental changes and the faceless threat of antibiotic resistance are currently among the top global health challenges. Community understanding of health, diseases and medicines in relation to the changing environment is necessary to mitigate the impact of these changes on health and for prudent use of antibiotics. Objective  The objective is to explore community perceptions of infectious diseases, antibiotic use and antibiotic resistance in the context of environmental changes. Methods  A qualitative study was conducted among community members with various backgrounds in education, gender, age and occupation of two districts of Odisha, India. Eight focus groups discussions and ten individual interviews were conducted. Data were analysed using content analysis. Results  Two themes emerged: ‘Interpretation of infectious diseases and health hazards in the context of environmental changes’, and ‘Understanding of antibiotic use and its consequences for resistance development and the environment’. The participants perceived that nowadays there is irregularity in the occurrence of seasons, particularly an increase in average temperature, which is influencing health. Participants’ perceptions of infectious diseases, antibiotic use and resistance varied according to their social environment. Furthermore, they perceived that improved sanitation, choice of alternative medicine and awareness and education on prudent use of antibiotics are probably some ways to prevent antibiotic resistance. Conclusions  The participants perceived that climate variability is increasing and that this has health consequences for the community. They also hypothesized an interrelationship between the environment, infectious diseases and medicine use, particularly antibiotics. This is helpful for further empirical studies. PMID:22583645

Community perceptions of infectious diseases, antibiotic use and antibiotic resistance in context of environmental changes: a study in Odisha, India.

PubMed

Sahoo, Krushna Chandra; Tamhankar, Ashok J; Johansson, Eva; Stålsby Lundborg, Cecilia

2014-10-01

The public health impact of environmental changes and the faceless threat of antibiotic resistance are currently among the top global health challenges. Community understanding of health, diseases and medicines in relation to the changing environment is necessary to mitigate the impact of these changes on health and for prudent use of antibiotics. The objective is to explore community perceptions of infectious diseases, antibiotic use and antibiotic resistance in the context of environmental changes. A qualitative study was conducted among community members with various backgrounds in education, gender, age and occupation of two districts of Odisha, India. Eight focus groups discussions and ten individual interviews were conducted. Data were analysed using content analysis. Two themes emerged: 'Interpretation of infectious diseases and health hazards in the context of environmental changes', and 'Understanding of antibiotic use and its consequences for resistance development and the environment'. The participants perceived that nowadays there is irregularity in the occurrence of seasons, particularly an increase in average temperature, which is influencing health. Participants' perceptions of infectious diseases, antibiotic use and resistance varied according to their social environment. Furthermore, they perceived that improved sanitation, choice of alternative medicine and awareness and education on prudent use of antibiotics are probably some ways to prevent antibiotic resistance. The participants perceived that climate variability is increasing and that this has health consequences for the community. They also hypothesized an interrelationship between the environment, infectious diseases and medicine use, particularly antibiotics. This is helpful for further empirical studies. © 2012 John Wiley & Sons Ltd.

Assessment of antibiotic use in farm animals in Rwanda.

PubMed

Manishimwe, Rosine; Nishimwe, Kizito; Ojok, Lonzy

2017-08-01

The irrational use of antibiotics in humans and animals is highly related to the emergence and increase of antibiotic-resistant bacteria worldwide. A cross-sectional survey aimed at evaluating the current level of practices regarding antibiotic use in farm animals in Rwanda was carried out countrywide. Interviews were conducted on 229 farmers rearing different types of animals. The study has revealed that almost all respondent farmers could name at least one antibiotic used in farm animals and peni-streptomycin was named by most of them (95.6%). The use of antibiotics in farm animals was observed in the majority of respondents (97.4%). It was found that 44.4 and 26.5% of respondents reported that they used antibiotics for disease prevention and growth promotion, respectively. The use of non-prescribed antibiotics in animals was also reported by more than the half of respondent farmers (55.6%). The majority of farmers had a moderate level of practices regarding antibiotic use in farm animals (73.5%), very few had a high level (26%) and only one respondent had a low level. The high level of practices in regard to antibiotic use in animals was associated with the location of the farm, the type of reared animals, and the rearing system. The results of this study give an insight into antibiotics usage practices in farm animals in Rwanda. The generated information can guide sensitizations and promotions of the prudent use of antibiotics among farmers in order to limit the increase of antibiotic resistance in the country.

Resistance to antibiotics in the normal flora of animals.

PubMed

Sørum, H; Sunde, M

2001-01-01

The normal bacterial flora contains antibiotic resistance genes to various degrees, even in individuals with no history of exposure to commercially prepared antibiotics. Several factors seem to increase the number of antibiotic-resistant bacteria in feces. One important factor is the exposure of the intestinal flora to antibacterial drugs. Antibiotics used as feed additives seem to play an important role in the development of antibiotic resistance in normal flora bacteria. The use of avoparcin as a feed additive has demonstrated that an antibiotic considered "safe" is responsible for increased levels of antibiotic resistance in the normal flora enterococci of animals fed with avoparcin and possibly in humans consuming products from these animals. However, other factors like stress from temperature, crowding, and management also seem to contribute to the occurrence of antibiotic resistance in normal flora bacteria. The normal flora of animals has been studied with respect to the development of antibiotic resistance over four decades, but there are few studies with the intestinal flora as the main focus. The results of earlier studies are valuable when focused against the recent understanding of mobile genetics responsible for bacterial antibiotic resistance. New studies should be undertaken to assess whether the development of antibiotic resistance in the normal flora is directly linked to the dramatic increase in antibiotic resistance of bacterial pathogens. Bacteria of the normal flora, often disregarded scientifically, should be studied with the intention of using them as active protection against infectious diseases and thereby contributing to the overall reduction of use of antibioties in both animals and humans.

Generic antibiotics in Japan.

PubMed

Fujimura, Shigeru; Watanabe, Akira

2012-08-01

Generic drugs have been used extensively in many developed countries, although their use in Japan has been limited. Generic drugs reduce drug expenses and thereby national medical expenditure. Because generic drugs provide advantages for both public administration and consumers, it is expected that they will be more widely used in the future. However, the diffusion rate of generic drugs in Japan is quite low compared with that of other developed countries. An investigation on generic drugs conducted by the Ministry of Health, Labour and Welfare in Japan revealed that 17.2 % of doctors and 37.2 % of patients had not used generic drugs. The major reasons for this low use rate included distrust of off-patent products and lower drug price margin compared with the brand name drug. The generic drugs available in the market include external drugs such as wet packs, antihypertensive agents, analgesics, anticancer drugs, and antibiotics. Among them, antibiotics are frequently used in cases of acute infectious diseases. When the treatment of these infections is delayed, the infection might be aggravated rapidly. The pharmacokinetics-pharmacodynamics (PK-PD) theory has been adopted in recent chemotherapy, and in many cases, the most appropriate dosage and administration of antibiotics are determined for individual patients considering renal function; high-dosage antibiotics are used preferably for a short duration. Therefore, a highly detailed antimicrobial agent is necessary. However, some of the generic antibiotics have less antibacterial potency or solubility than the brand name products. We showed that the potency of the generic products of vancomycin and teicoplanin is lower than that of the branded drugs by 14.6 % and 17.3 %, respectively. Furthermore, we confirmed that a generic meropenem drug for injection required about 82 s to solubilize in saline, whereas the brand product required only about 21 s. It was thought that the cause may be the difference in size of bulk

Antibiotics for whooping cough (pertussis).

PubMed

Altunaiji, S; Kukuruzovic, R; Curtis, N; Massie, J

2007-07-18

Whooping cough is a highly contagious disease. Infants are at highest risk of severe disease and death. Erythromycin for 14 days is currently recommended for treatment and contact prophylaxis, but is of uncertain benefit. To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 1, 2007); MEDLINE (January 1966 to March 2007); EMBASE (January 1974 to March 2007). All randomised and quasi-randomised controlled trials of antibiotics for treatment of, and contact prophylaxis against, whooping cough. Three to four review authors independently extracted data and assessed the quality of each trial. Thirteen trials with 2197 participants met the inclusion criteria: 11 trials investigated treatment regimens; 2 investigated prophylaxis regimens. The quality of the trials was variable.Short-term antibiotics (azithromycin for three to five days, or clarithromycin or erythromycin for seven days) were as effective as long-term (erythromycin for 10 to 14 days) in eradicating Bordetella pertussis (B. pertussis) from the nasopharynx (relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05), but had fewer side effects (RR 0.66, 95% CI 0.52 to 0.83). Trimethoprim/sulfamethoxazole for seven days was also effective. Nor were there differences in clinical outcomes or microbiological relapse between short and long-term antibiotics. Contact prophylaxis of contacts older than six months of age with antibiotics did not significantly improve clinical symptoms or the number of cases developing culture-positive B. pertussis. Although antibiotics were effective in eliminating B. pertussis, they did not alter the subsequent clinical course of the illness. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

Dissemination of health information through social networks: Twitter and antibiotics

PubMed Central

Scanfeld, Vanessa; Larson, Elaine L.

2010-01-01

Background This study reviewed Twitter status updates mentioning “antibiotic(s)” to determine overarching categories and explore evidence of misunderstanding or misuse of antibiotics. Methods One thousand Twitter status updates mentioning antibiotic(s) were randomly selected for content analysis and categorization. To explore cases of potential misunderstanding or misuse, these status updates were mined for co-occurrence of the following terms: “cold + antibiotic(s),” “extra antibiotic(s),” “flu + antibiotic(s),” “leftover antibiotic(s),” and “share antibiotic(s)” and reviewed to confirm evidence of misuse or misunderstanding. Results Of the 1,000 status updates, 971 were categorized into 11 groups: General Use (n=289), Advice/Information (n=157), Side Effects/Negative Reactions (n=113), Diagnosis (n=102), Resistance (n=92), Misunderstanding and/or Misuse (n=55), Positive Reactions (n=48), Animals (n=46), Other (n=42), Wanting/Needing (n=19), and Cost (n=8). Cases of misunderstanding or abuse were identified for the following combinations: “flu + antibiotic(s)” (n=345), “cold + antibiotic(s)” (n=302), “leftover antibiotic(s)” (n=23), “share antibiotic(s)” (n=10), and “extra antibiotic(s)” (n=7). Conclusions Social media sites offer means of health information sharing. Further study is warranted to explore how such networks may provide a venue to identify misuse or misunderstanding of antibiotics, promote positive behavior change, disseminate valid information, and explore how such tools can be used to gather real-time health data. PMID:20347636

Procalcitonin-guided antibiotic treatment in critically ill patients.

PubMed

Hohn, Andreas; Heising, Bernhard; Schütte, Jan-Karl; Schroeder, Olaf; Schröder, Stefan

2017-02-01

In critically ill patients, length of antibiotic treatment can be effectively guided by procalcitonin (PCT) protocols. International sepsis guidelines and guidelines on antibiotic stewardship strategies recommend PCT as helpful laboratory marker for a rational use of antibiotics. A number of studies and meta-analyses have confirmed the effectiveness of PCT-protocols for shortening antibiotic treatment without compromising clinical outcome in critically ill patients. But in clinical practice, there is still uncertainty how to interpret PCT levels and how to adjust antibiotic treatment in various infectious situations, especially in the perioperative period. This narrative review gives an overview on the application of PCT-protocols in critically ill patients with severe bacterial infections on the basis of 5 case reports and the available literature. Beside strengths and limitations of this biomarker, also varying kinetics and different maximum values with regard to the infectious focus and pathogens are discussed. PCT-guided antibiotic treatment appears to be safe and effective. Most of the studies revealed a shorter antibiotic treatment without negative clinical outcomes. Cost effectiveness is still a matter of debate and effects on bacterial resistance due to shorter treatments, possible lower rates of drug-related adverse events, or decreased rates of Clostridium difficile infections are not yet evaluated. Guidance of antibiotic treatment can effectively be supported by PCT-protocols. However, it is important to consider the limitations of this biomarker and to use PCT protocols along with antibiotic stewardship programmes and regular clinical rounds together with infectious diseases specialists.

Noise analysis of antibiotic permeation through bacterial channels

NASA Astrophysics Data System (ADS)

Nestorovich, Ekaterina M.; Danelon, Christophe; Winterhalter, Mathias; Bezrukov, Sergey M.

2003-05-01

Statistical analysis of high-resolution current recordings from a single ion channel reconstituted into a planar lipid membrane allows us to study transport of antibiotics at the molecular detail. Working with the general bacterial porin, OmpF, we demonstrate that addition of zwitterionic β-lactam antibiotics to the membrane-bathing solution introduces transient interruptions in the small-ion current through the channel. Time-resolved measurements reveal that one antibiotic molecule blocks one of the monomers in the OmpF trimer for characteristic times from microseconds to hundreds of microseconds. Spectral noise analysis enables us to perform measurements over a wide range of changing parameters. In all cases studied, the residence time of an antibiotic molecule in the channel exceeds the estimated time for free diffusion by orders of magnitude. This demonstrates that, in analogy to substrate-specific channels that evolved to bind specific metabolite molecules, antibiotics have 'evolved' to be channel-specific. The charge distribution of an efficient antibiotic complements the charge distribution at the narrowest part of the bacterial porin. Interaction of these charges creates a zone of attraction inside the channel and compensates the penetrating molecule's entropy loss and desolvation energy. This facilitates antibiotic translocation through the narrowest part of the channel and accounts for higher antibiotic permeability rates.

When and How to Take Antibiotics

MedlinePlus

... Work Contact Us ABOUT THE ISSUE What is Antibiotic Resistance? General Background Science of Resistance Glossary References POLICY ... for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance Project (ROAR) INTERNATIONAL CHAPTERS APUA Chapter Network Africa ...

Short-course antibiotics for acute otitis media.

PubMed

Kozyrskyj, Anita; Klassen, Terry P; Moffatt, Michael; Harvey, Krystal

2010-09-08

Acute otitis media (AOM) is a common illness during childhood, for which antibiotics are frequently prescribed. To determine the effectiveness of a short course of antibiotics (less than seven days) in comparison to a long course of antibiotics (seven days or greater) for the treatment of AOM in children. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 4) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, CINAHL, BIOSIS Previews, OCLC Papers First and Proceedings First, Proquest Dissertations and Theses (inception to November 2009); International Pharmaceutical Abstracts, the NLM Gateway, ClinicalTrials.gov and Current Controlled Trials (inception to August 2008). Trials were included if they met the following criteria: participants aged one month to 18 years; clinical diagnosis of ear infection; no previous antimicrobial therapy; and randomisation to treatment with less than seven days versus seven days or more of antibiotics. The primary outcome of treatment failure was defined as the absence of clinical resolution, relapse or recurrence of AOM during one month following initiation of therapy. Treatment outcomes were extracted from individual studies and combined in the form of a summary odds ratio (OR). A summary OR of 1.0 indicates that the treatment failure rate following less than seven days of antibiotic treatment was similar to the failure rate following seven days or more of treatment. This update included 49 trials containing 12,045 participants. Risk of treatment failure was higher with short courses of antibiotics (OR 1.34, 95% CI 1.15 to 1.55) at one month after initiation of therapy (21% failure with short-course treatment and 18% with long-course; absolute difference of 3% between groups). There were no differences found when examining treatment with ceftriaxone for less than seven days (30% failure

Reducing Parental Demand for Antibiotics by Promoting Communication Skills

ERIC Educational Resources Information Center

Alder, Stephen C.; Trunnell, Eric P.; White, George L., Jr.; Lyon, Joseph L.; Reading, James P.; Samore, Matthew H.; Magill, Michael K.

2005-01-01

Antibiotic-resistant strains of bacteria are continuing to emerge as high rates of antibiotic use persist. Children are among the highest users of antibiotics, with parents influencing physician decision-making regarding antibiotic prescription. An intervention based on Social Cognitive Theory (SCT) to reduce parents' expectations for antibiotics…

A Common Platform for Antibiotic Dereplication and Adjuvant Discovery.

PubMed

Cox, Georgina; Sieron, Arthur; King, Andrew M; De Pascale, Gianfranco; Pawlowski, Andrew C; Koteva, Kalinka; Wright, Gerard D

2017-01-19

Solving the antibiotic resistance crisis requires the discovery of new antimicrobial drugs and the preservation of existing ones. The discovery of inhibitors of antibiotic resistance, antibiotic adjuvants, is a proven example of the latter. A major difficulty in identifying new antibiotics is the frequent rediscovery of known compounds, necessitating laborious "dereplication" to identify novel chemical entities. We have developed an antibiotic resistance platform (ARP) that can be used for both the identification of antibiotic adjuvants and for antibiotic dereplication. The ARP is a cell-based array of mechanistically distinct individual resistance elements in an identical genetic background. In dereplication mode, we demonstrate the rapid identification, and thus discrimination, of common antibiotics. In adjuvant discovery mode, we show that the ARP can be harnessed in screens to identify inhibitors of resistance. The ARP is therefore a powerful tool that has broad application in confronting the resistance crisis. Copyright © 2017 Elsevier Ltd. All rights reserved.

In-feed antibiotic effects on the swine intestinal microbiome

PubMed Central

Looft, Torey; Johnson, Timothy A.; Allen, Heather K.; Bayles, Darrell O.; Alt, David P.; Stedtfeld, Robert D.; Sul, Woo Jun; Stedtfeld, Tiffany M.; Chai, Benli; Cole, James R.; Hashsham, Syed A.; Tiedje, James M.; Stanton, Thad B.

2012-01-01

Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment, with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment, with the medicated pigs showing an increase in Proteobacteria (1–11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses. PMID:22307632

Randomized clinical trial of antibiotic therapy for uncomplicated appendicitis.

PubMed

Park, H C; Kim, M J; Lee, B H

2017-12-01

Uncomplicated appendicitis may resolve spontaneously or require treatment with antibiotics or appendicectomy. The aim of this randomized trial was to compare the outcome of a non-antibiotic management strategy with that of antibiotic therapy in uncomplicated appendicitis. Patients presenting to a university teaching hospital with CT-verified uncomplicated simple appendicitis (appendiceal diameter no larger than 11 mm and without any signs of perforation) were randomized to management with a no-antibiotic regimen with supportive care (intravenous fluids, analgesia and antipyretics as necessary) or a 4-day course of antibiotics with supportive care. The primary endpoint was rate of total treatment failure, defined as initial treatment failure within 1 month and recurrence of appendicitis during the follow-up period. Some 245 patients were randomized within the trial, and followed up for a median of 19 months. The duration of hospital stay was shorter (mean 3·1 versus 3·7 days; P < 0·001) and the medical costs lower (€1181 versus 1348; P < 0·001) among those randomized to therapy without antibiotics. There was no difference in total treatment failure rate between the groups: 29 of 124 (23·4 per cent) in the no-antibiotic group and 25 of 121 (20·7 per cent) in the antibiotic group (P = 0·609). Eighteen patients (9 in each group) had initial treatment failure, 15 of whom underwent appendicectomy and three received additional antibiotics. Thirty-six patients (20 in the no-antibiotic group, 16 in the antibiotic group) experienced recurrence, of whom 30 underwent appendicectomy and six received further antibiotics. Treatment failure rates in patients presenting with CT-confirmed uncomplicated appendicitis appeared similar among those receiving supportive care with either a no-antibiotic regimen or a 4-day course of antibiotics. Registration number: KCT0000124 ( http://cris.nih.go.kr). © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

The Antibiotic Resistance Problem Revisited

ERIC Educational Resources Information Center

Lawson, Michael A.

2008-01-01

The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how…

Nonmedical Uses of Antibiotics: Time to Restrict Their Use?

PubMed Central

Meek, Richard William; Vyas, Hrushi; Piddock, Laura Jane Violet

2015-01-01

The global crisis of antibiotic resistance has reached a point where, if action is not taken, human medicine will enter a postantibiotic world and simple injuries could once again be life threatening. New antibiotics are needed urgently, but better use of existing agents is just as important. More appropriate use of antibiotics in medicine is vital, but the extensive use of antibiotics outside medical settings is often overlooked. Antibiotics are commonly used in animal husbandry, bee-keeping, fish farming and other forms of aquaculture, ethanol production, horticulture, antifouling paints, food preservation, and domestically. This provides multiple opportunities for the selection and spread of antibiotic-resistant bacteria. Given the current crisis, it is vital that the nonmedical use of antibiotics is critically examined and that any nonessential use halted. PMID:26444324

Nonmedical Uses of Antibiotics: Time to Restrict Their Use?

PubMed

Meek, Richard William; Vyas, Hrushi; Piddock, Laura Jane Violet

2015-10-01

The global crisis of antibiotic resistance has reached a point where, if action is not taken, human medicine will enter a postantibiotic world and simple injuries could once again be life threatening. New antibiotics are needed urgently, but better use of existing agents is just as important. More appropriate use of antibiotics in medicine is vital, but the extensive use of antibiotics outside medical settings is often overlooked. Antibiotics are commonly used in animal husbandry, bee-keeping, fish farming and other forms of aquaculture, ethanol production, horticulture, antifouling paints, food preservation, and domestically. This provides multiple opportunities for the selection and spread of antibiotic-resistant bacteria. Given the current crisis, it is vital that the nonmedical use of antibiotics is critically examined and that any nonessential use halted.

Antibiotic prophylaxis for operative vaginal delivery.

PubMed

Liabsuetrakul, Tippawan; Choobun, Thanapan; Peeyananjarassri, Krantarat; Islam, Q Monir

2014-10-13

Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps deliveries, or both. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2014). All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Two review authors assessed trial eligibility and methodological quality. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. For this update, we assessed methodological quality of the one included trial using the standard Cochrane criteria and the GRADE approach. We calculated the risk ratio (RR) and mean difference (MD) using a fixed-effect model and all the review authors interpreted and discussed the results. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. This trial identified only two out of the nine outcomes specified in this review. It reported seven women with endomyometritis in the

Antibiotic prophylaxis for operative vaginal delivery.

PubMed

Liabsuetrakul, T; Choobun, T; Peeyananjarassri, K; Islam, M

2004-01-01

Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics are prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum and/or forceps deliveries. We searched the Cochrane Pregnancy and Childbirth Group trials register (November 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003) and MEDLINE (1966 to November 2003). All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Four reviewers assessed trial eligibility and methodological quality. Two reviewers extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all reviewers. We assessed methodological quality of the included trial using the standard Cochrane criteria and the CONSORT statement of randomised controlled trials. We calculated the relative risks using a fixed effect model and all the reviewers interpreted and discussed the results. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. This trial identified only two out of the nine

Antibiotics detected in urines and adipogenesis in school children.

PubMed

Wang, Hexing; Wang, Na; Wang, Bin; Fang, Hong; Fu, Chaowei; Tang, Chuanxi; Jiang, Feng; Zhou, Ying; He, Gengsheng; Zhao, Qi; Chen, Yue; Jiang, Qingwu

2016-01-01

Although antibiotic use during early life has been demonstrated to be related to the altered adipogenesis in later life, limited data are available for the effect of antibiotic exposure in school children on adiposity from various sources, including from the use or contaminated food or drinking water. To explore the association between the internal exposure of antibiotics from various sources and adipogenesis in school children using the biomonitoring of urinary antibiotics. After 586 school children aged 8-11years were selected from Shanghai in 2013, total urinary concentrations (free and conjugated) of 21 common antibiotics from six categories (macrolides, β-lactams, tetracyclines, fluoroquinolones, sulfonamides, and phenicols), including five human antibiotics (HAs), two antibiotics preferred as HA, four veterinary antibiotics (VAs), and ten antibiotics preferred as VA, were measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Creatinine-corrected urinary concentrations of antibiotics were used to assess their exposure. Overweight or obesity was determined by the body mass index or waist circumference-based criteria deriving from national data. All 21 antibiotics were found in urines with the overall detection frequency of 79.6%. The multinomial logistic regression analyses showed the significant associations of overweight and obesity with the exposure to VAs and antibiotics preferred as VA, but not with HAs or antibiotics preferred as HA. After adjusted for a number of obesity-relevant variables, the odds ratios (95% confidence interval) of BMI-based obesity risk of tertiles 2 and 3 of urinary concentrations relative to tertile 1 were respectively 2.54 (1.27, 5.07) and 2.92 (1.45, 5.87) for florfenicol, 0.57 (0.12, 2.63) and 3.63 (1.41, 9.32) for trimethoprim, and 3.00 (1.56, 5.76) and 1.99 (0.99, 4.01) for sum of veterinary antibiotics. Similar results were found when the outcome used WC-based obesity

Use of antibiotic beads to salvage infected breast implants.

PubMed

Sherif, Rami D; Ingargiola, Michael; Sanati-Mehrizy, Paymon; Torina, Philip J; Harmaty, Marco A

2017-10-01

When an implant becomes infected, implant salvage is often performed where the implant is removed, capsulectomy is performed, and a new implant is inserted. The patient is discharged with a PICC line and 6-8 weeks of intravenous (IV) antibiotics. This method has variable success and subjects the patient to long-term systemic antibiotics. In the 1960s, the use of antibiotic-impregnated beads for the treatment of chronic osteomyelitis was described. These beads deliver antibiotic directly to the site of the infection, thereby eliminating the complications of systemic IV antibiotics. This study aimed to present a case series illustrating the use of STIMULAN calcium sulfate beads loaded with vancomycin and tobramycin to increase the rate of salvage of the infected implant and forgo IV antibiotics. A retrospective analysis was performed of patients who were treated at Mount Sinai Hospital for implant infection with salvage and antibiotic beads. Twelve patients were identified, 10 of whom had breast cancer. Comorbidities included hypertension, smoking, and immunocompromised status. Infections were noted anywhere from 5 days to 8 years postoperatively. Salvage was successful in 9 out of the 12 infected implants using antibiotic bead therapy without home IV antibiotics. The use of antibiotic beads is promising for salvaging infected breast implants without IV antibiotics. Seventy-five percent of the implants were successfully salvaged. Of the three patients who had unsalvageable implants, one was infected with antibiotic-resistant Rhodococcus that was refractory to bead therapy and one was noncompliant with postoperative instructions. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

[Proper antibiotic therapy. From penicillin to pharmacogenomic].

PubMed

Caramia, G; Ruffini, E

2012-04-01

Antibiotics have always been considered one of the wonder discoveries of the 20th century. The use of penicillin by Flaming, opened up the golden era of antibiotics and now is hard to imagine the practice of medicine without antibiotics. Life-threatening infections, such as meningitis, endocarditis, bacteremic pneumonia sepsis, would again prove fatal. Also aggressive chemotherapy and transplant procedures would prove impossible. Another real wonder has been the rise of antibiotic resistance soon after the clinical use of penicillin in hospitals and communities. Several study demonstrated an excessive amount of antibiotic prescribing for communities patients and inpatients and in some hospital up to 50% of antibiotic usage is inappropriate: the benefits of antibiotic treatment come with the risk of antibiotic resistance development. In hospitals, infections caused by antibiotic-resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic-susceptible bacteria. A variety of strategies has been proposed to reduce the cost and improve the quality of medication use. Education, guidelines and evidence based recommendations are considered to be essential elements of any program designed to influence prescribing behavior and can provide a foundation of knowledge that will enhance and increase the acceptance of stewardship strategies. Evidence-based recommendations, an approach to clinical practice helping to make decisions based on clinical expertise and on intimate knowledge of the individual patient's situations, beliefs, and priorities, enhance antimicrobial stewardship, that include appropriate selection, dosing, route, and duration of antimicrobial therapy can maximize clinical cure or prevention of infection while limiting the unintended consequences, such as the emergence of resistance, adverse drug events, and cost. These evidence-based guidelines are not a substitute for clinical

Historic perspective: prebiotics, probiotics, and other alternatives to antibiotics.

PubMed

Hume, M E

2011-11-01

Applications of antimicrobials in food production and human health have found favor throughout human history. Antibiotic applications in agricultural and human medical arenas have resulted in tremendous increases in food animal production and historically unprecedented gains in human health protection. Successes attributed to widespread antibiotic use have been accompanied by the inadvertent emergence of antibiotic-resistant bacteria. A major problem associated with this emerging resistance is the crossover use of some antibiotics in agricultural settings as well as in the prevention and treatment of human disease. This outcome led to calls to restrict the use of human health-related antibiotics in food animal production. Calls for restricted antibiotic use have heightened existing searches for alternatives to antibiotics that give similar or enhanced production qualities as highly reliable as the antibiotics currently provided to food animals. Agricultural and scientific advances, mainly within the last 100 yr, have given us insights into sources, structures, and actions of materials that have found widespread application in our modern world. The purpose of this presentation is to provide a historic perspective on the search for what are generally known as antibiotics and alternative antimicrobials, probiotics, prebiotics, bacteriophages, bacteriocins, and phytotherapeutics.

Regulation of veterinary antibiotics in Australia.

PubMed

Dyke, T M

2003-01-01

The Australian Pesticides and Veterinary Medicines Authority (APVMA)* registers veterinary antibiotic products before they can be supplied, distributed or sold in Australia. Extensive scientific assessment on all new veterinary antibiotic products is undertaken for the APVMA by experts in other government agencies including the Therapeutic Goods Administration (toxicology), the National Occupational Health and Safety Commission (occupational health and safety), Environment Australia (environmental hazards) and state departments of agriculture or primary industry (efficacy and safety) as well as APVMA assessments on food residues, trade and manufacturing. The National Health and Medical Research Council Expert Advisory Group on Antimicrobial Resistance provides advice to the APVMA on the potential transfer of antibiotic resistance from the use of antibiotics in animals to humans, and the impact transfer may have on public health. Food Standards Australia New Zealand (previously Australia New Zealand Food Authority) set maximum residue levels for human foods. The APVMA monitors registered product use through compliance activities and an adverse experience reporting program, and reviews registered products as necessary. The import, manufacture, supply and use of veterinary antibiotics are regulated by Commonwealth and State governments in Australia.

Medical Treatment of Diverticular Disease: Antibiotics.

PubMed

Lué, Alberto; Laredo, Viviana; Lanas, Angel

2016-10-01

Diverticular disease (DD) of the colon represents the most common disease affecting the large bowel in western countries. Its prevalence is increasing. Recent studies suggest that changes in gut microbiota could contribute to development of symptoms and complication. For this reason antibiotics play a key role in the management of both uncomplicated and complicated DD. Rifaximin has demonstrated to be effective in obtaining symptoms relief at 1 year in patients with uncomplicated DD and to improve symptoms and maintain periods of remission following acute colonic diverticulitis (AD). Despite absence of data that supports the routine use of antibiotic in uncomplicated AD, they are recommended in selected patients. In patients with AD that develop an abscess, conservative treatment with broad-spectrum antibiotics is successful in up to 70% of cases. In patients on conservative treatment where percutaneous drainage fails or peritonitis develops, surgery is considered the standard therapy. In conclusion antibiotics seem to remain the mainstay of treatment in symptomatic uncomplicated DD and AD. Inpatient management and intravenous antibiotics are necessary in complicated AD, while outpatient management is considered the best strategy in the majority of uncomplicated patients.

The Search for 'Evolution-Proof' Antibiotics.

PubMed

Bell, Graham; MacLean, Craig

2018-06-01

The effectiveness of antibiotics has been widely compromised by the evolution of resistance among pathogenic bacteria. It would be restored by the development of antibiotics to which bacteria cannot evolve resistance. We first discuss two kinds of 'evolution-proof' antibiotic. The first comprises literally evolution-proof antibiotics to which bacteria cannot become resistant by mutation or horizontal gene transfer. The second category comprises agents to which resistance may arise, but so rarely that it does not become epidemic. The likelihood that resistance to a novel agent will spread is evaluated here by a simple model that includes biological and therapeutic parameters governing the evolution of resistance within hosts and the transmission of resistant strains between hosts. This model leads to the conclusion that epidemic spread is unlikely if the frequency of mutations that confer resistance falls below a defined minimum value, and it identifies potential targets for intervention to prevent the evolution of resistance. Whether or not evolution-proof antibiotics are ever found, searching for them is likely to improve the deployment of new and existing agents by advancing our understanding of how resistance evolves. Copyright © 2017. Published by Elsevier Ltd.

Fate of Antibiotic Resistant Bacteria and Genes during Wastewater Chlorination: Implication for Antibiotic Resistance Control

PubMed Central

Yuan, Qing-Bin; Guo, Mei-Ting; Yang, Jian

2015-01-01

This study investigated fates of nine antibiotic-resistant bacteria as well as two series of antibiotic resistance genes in wastewater treated by various doses of chlorine (0, 15, 30, 60, 150 and 300 mg Cl2 min/L). The results indicated that chlorination was effective in inactivating antibiotic-resistant bacteria. Most bacteria were inactivated completely at the lowest dose (15 mg Cl2 min/L). By comparison, sulfadiazine- and erythromycin-resistant bacteria exhibited tolerance to low chlorine dose (up to 60 mg Cl2 min/L). However, quantitative real-time PCRs revealed that chlorination decreased limited erythromycin or tetracycline resistance genes, with the removal levels of overall erythromycin and tetracycline resistance genes at 0.42 ± 0.12 log and 0.10 ± 0.02 log, respectively. About 40% of erythromycin-resistance genes and 80% of tetracycline resistance genes could not be removed by chlorination. Chlorination was considered not effective in controlling antimicrobial resistance. More concern needs to be paid to the potential risk of antibiotic resistance genes in the wastewater after chlorination. PMID:25738838

Inhaled Antibiotics for Gram-Negative Respiratory Infections

PubMed Central

Fraidenburg, Dustin R.; Scardina, Tonya

2016-01-01

SUMMARY Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena. PMID:27226088

Explaining family physicians’ beliefs about antibiotic prescription

PubMed Central

Shokouhi, Elham; Zamani-Alavijeh, Fereshteh; Araban, Marzieh

2017-01-01

Background Antibiotics are among those drugs prescribed abundantly in hospitals due to their high efficiency. However, excessive, non-logical and unnecessary use of antibiotics regardless of physicians’ recommendations is considered as a challenge. Objectives The aim of this study was to explain family physicians’ beliefs about antibiotic prescription in Ahvaz. Methods This study is part of a content-analysis qualitative research conducted in Ahvaz in 2016. Study subjects were selected according to purposive sampling and data collection continued to data saturation. Required data were collected using semi-structured in-depth interviews with participation of eight subjects. Data analysis was conducted along with conducting interviews using constant comparison analysis, and it continued to the last interview. Strength and accuracy of data were investigated by experts and participants. Results From data analysis, four major categories were extracted that were composed of 20 subcategories. They were 1) expected outcomes of antibiotics (perceived pros and cons); 2) perceived pressure to follow others’ opinions; 3) the level of access to antibiotics; and 4) individual’s perception for prescription. Conclusion Findings of this study showed that various factors affect physicians’ decisions to prescribe antibiotics and it is emphasized to consider these factors. PMID:29238498

Inhaled Antibiotics for Gram-Negative Respiratory Infections.

PubMed

Wenzler, Eric; Fraidenburg, Dustin R; Scardina, Tonya; Danziger, Larry H

2016-07-01

Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Antibiotic Stewardship: New Frontier, Familiar Journey.

PubMed

Martin, Caren McHenry

2017-05-01

Recent changes in regulations by the Centers for Medicare & Medicaid Services require long-term care facilities to meet specific requirements on antibiotic stewardship, promoting the appropriate use of antibiotics and antimicrobials. The goal is to improve patient outcomes and decrease the spread of infections caused by multi-drug-resistant organisms. Consultant pharmacists can help facility personnel implement policies and procedures for effective antibiotic stewardship, assist prescribers and facility staff in understanding how to use the facility's antibiogram, find appropriate resources, and provide facility personnel with feedback on their antimicrobial stewardship efforts.

US antibiotic stewardship and penicillin allergy.

PubMed

Wada, Kara J; Calhoun, Karen H

2017-06-01

The purpose of this review is to improve otolaryngologists' antibiotic stewardship by detailing current approaches to penicillin allergy. Although up to 15% of hospitalized patients in the United States have a penicillin allergy recorded on their charts, fewer than 10% of these have a true penicillin allergy. Using a combination of a detailed allergy history, skin testing and graded-dose administration, many patients whose charts say 'penicillin-allergic' can safely be treated with penicillin and cross-reacting antibiotics. This permits use of narrower-spectrum antibiotics and saves money.

Demonstrating Effectiveness of Antibiotics Against Known Bacteria Strains

ERIC Educational Resources Information Center

Keefe, Lois M.

1977-01-01

Procedures are described for showing the effectiveness of antibiotics (penicillin, ampicillin, and tetracycline) against a nonpathogenic bacteria strain (Bacillus cereus). Methods are outlined for preparing nutrient agar, sterilizing tubes, pouring agar plates, preparing antibiotic discs, and transferring antibiotic discs to agar plates. (CS)

[Paths to the professional and responsible use of antibiotics].

PubMed

Abele-Horn, Marianne; Pantke, Ellen; Eckmanns, Tim

2018-05-01

Germany's position on prescribing antibiotics is among the lower third in Europe. There are some countries that prescribe remarkably fewer antibiotics. In Germany, the number of out-patient antibiotic prescriptions is too high for patients with low-grade infections and non-bacterial infections. Often, broad-spectrum antibiotics are prescribed instead of narrow-spectrum antibiotics. For in-patients, perioperative prophylaxis is given for too long.In this article, different ways to reduce antibiotic prescriptions are introduced. Recommendations are given to improve the quality of therapy, implementation of diagnostics and scores, as well as information for physicians and patients.In this regard, an unsystematic literature search was done.To optimise the quality of prescribing, antibiotic checklists should be used. The important initial questions are if there is a bacterial infection and if antibiotic therapy is necessary. To apply diagnostics correctly is essential. Antibiotic use can be shortened or in some cases totally omitted if point-of-care tests (POCTs) are applied correctly. Species identification and resistance testing are essential for quality assurance. S3-guidelines are central for modern evidence-based medicine. Another key factor is good communication within the team and with patients. All measurements, like the application of POCTs, back-up prescribing, and prescribing an antibiotic, have to be communicated in a clear and sensitive way.

Determinants of between-country differences in ambulatory antibiotic use and antibiotic resistance in Europe: a longitudinal observational study.

PubMed

Blommaert, A; Marais, C; Hens, N; Coenen, S; Muller, A; Goossens, H; Beutels, P

2014-02-01

To identify key determinants explaining country-year variations in antibiotic use and resistance. Ambulatory antibiotic use data [in defined daily doses per 1000 inhabitants per day (DIDs)] for 19 European countries from 1999 to 2007 were collected, along with 181 variables describing countries in terms of their agriculture, culture, demography, disease burden, education, healthcare organization and socioeconomics. After assessing data availability, overlap and relevance, multiple imputation generalized estimating equations were applied with a stepwise selection procedure to select significant determinants of global antibiotic use (expressed in DIDs), relative use of subgroups (amoxicillin and co-amoxiclav) and resistance of Escherichia coli and Streptococcus pneumoniae. Relative humidity, healthcare expenditure proportional to gross domestic product, feelings of distrust, proportion of population aged >65 years and availability of treatment guidelines were associated with higher total antibiotic use expressed in DIDs. Restrictions on marketing activities towards prescribers, population density, number of antibiotics, educational attainment and degree of atheism were associated with a lower number of total DIDs used. Relative prescribing of amoxicillin and co-amoxiclav was mainly determined by healthcare system choices [e.g. general practitioner (GP) registration and restricted marketing]. Specific antibiotic use was found to be a significant determinant of resistance for some but not all drug/organism combinations. Incentives to stimulate GP gatekeeping were associated with lower levels of resistance, and life expectancy at age 65+ and atheism were associated with more resistance. Myriad factors influence antibiotic use and resistance at the country level and an important part of these can be modified by policy choices.

Antibiotic resistance: a primer and call to action.

PubMed

Smith, Rachel A; M'ikanatha, Nkuchia M; Read, Andrew F

2015-01-01

During the past century, discoveries of microorganisms as causes of infections and antibiotics as effective therapeutic agents have contributed to significant gains in public health in many parts of the world. Health agencies worldwide are galvanizing attention toward antibiotic resistance, which is a major threat to public health (Centers for Disease Control and Prevention, 2013; World Health Organization, 2014). Some life scientists believe that we are approaching the post-antibiotic age (Davies & Davies, 2010). The growing threat of antimicrobial resistance is fueled by complex factors with biological, behavioral, and societal aspects. This primer provides an overview of antibiotic resistance and its growing burden on public health, the biological and behavioral mechanisms that increase antibiotic resistance, and examples of where health communication scholars can contribute to efforts to make our current antibiotic drugs last as long as possible. In addition, we identify compelling challenges for current communication theories and practices.

Antibiotic prophylaxia in patients with severe acute pancreatitis.

PubMed

Zhou, Yan-Ming; Xue, Zuo-Liang; Li, Yu-Min; Zhu, You-Quan; Cao, Nong

2005-02-01

The prophylactic use of antibiotics in patients with severe acute pancreatitis remains contentious. This study was undertaken to review the current studies on antibiotic prophylaxis in patients with severe acute pancreatitis. All papers found by a Medline search were relevant to human trials of antibiotic prophylaxis in patients with severe acute pancreatitis. In the 1970s, three small randomized studies of prophylactic ampicillin in the treatment of acute pancreatitis showed no effect on mortality or morbidity, but the inclusion of patients at low risk for infection and the use of an ineffective antibiotic were insufficient to detect any differences. From 1993 to 2001, eight prospective clinical trials of antibiotic prophylaxis were conducted in patients with severe acute pancreatitis (SAP). Seven of the 8 trials showed significant effect of the prophylaxis in prevention of pancreatic infections, and one showed significant improvement of clinical course documented by the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Only two trials did demonstrate the significance of the prophylaxis in lowering the mortality rate. Despite variations in drug agents, study size and patient selection, duration of treatment, and methodology (None of the studies was double-blinded), a meta-analysis showed the positive effect of antibiotics in reducing the mortality. We suggested that antibiotic prophylaxis with proven efficacy in necrotic pancreatic tissues should be given to all patients with acute necrotizing pancreatitis. In recent years, however, the first double-blind, placebo-controlled multicenter study from Germany detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis. Prophylactic antibiotics for severe acute pancreatitis is still a matter of discussion and further studies are required to provide adequate data to answer many questions and to define the role of antibiotic prophylaxis in patients

Assessing the antibiotic susceptibility of freshwater Cyanobacteria spp.

PubMed Central

Dias, Elsa; Oliveira, Micaela; Jones-Dias, Daniela; Vasconcelos, Vitor; Ferreira, Eugénia; Manageiro, Vera; Caniça, Manuela

2015-01-01

Freshwater is a vehicle for the emergence and dissemination of antibiotic resistance. Cyanobacteria are ubiquitous in freshwater, where they are exposed to antibiotics and resistant organisms, but their role on water resistome was never evaluated. Data concerning the effects of antibiotics on cyanobacteria, obtained by distinct methodologies, is often contradictory. This emphasizes the importance of developing procedures to understand the trends of antibiotic susceptibility in cyanobacteria. In this study we aimed to evaluate the susceptibility of four cyanobacterial isolates from different genera (Microcystis aeruginosa, Aphanizomenon gracile, Chrisosporum bergii, Planktothix agradhii), and among them nine isolates from the same specie (M. aeruginosa) to distinct antibiotics (amoxicillin, ceftazidime, ceftriaxone, kanamycine, gentamicine, tetracycline, trimethoprim, nalidixic acid, norfloxacin). We used a method adapted from the bacteria standard broth microdilution. Cyanobacteria were exposed to serial dilution of each antibiotic (0.0015–1.6 mg/L) in Z8 medium (20 ± 1°C; 14/10 h L/D cycle; light intensity 16 ± 4 μEm−2s−1). Cell growth was followed overtime (OD450nm/microscopic examination) and the minimum inhibitory concentrations (MICs) were calculated for each antibiotic/isolate. We found that β-lactams exhibited the lower MICs, aminoglycosides, tetracycline and norfloxacine presented intermediate MICs; none of the isolates were susceptible to trimethoprim and nalidixic acid. The reduced susceptibility of all tested cyanobacteria to some antibiotics suggests that they might be naturally non-susceptible to these compounds, or that they might became non-susceptible due to antibiotic contamination pressure, or to the transfer of genes from resistant bacteria present in the environment. PMID:26322027

Worldwide pattern of antibiotic prescription in endodontic infections.

PubMed

Segura-Egea, Juan José; Martín-González, Jenifer; Jiménez-Sánchez, María Del Carmen; Crespo-Gallardo, Isabel; Saúco-Márquez, Juan José; Velasco-Ortega, Eugenio

2017-08-01

Odontogenic infections, and especially endodontic infections, are polymicrobial, involving a combination of Gram-positive and Gram-negative facultative anaerobes and strictly anaerobic bacteria. Therefore, antibiotics can be used as an adjunct to endodontic treatment. However, most chronic and even acute endodontic infections can be successfully managed by disinfection of the root-canal system, which eliminates the source of infection, followed by abscess drainage or tooth extraction, without the need for antibiotics. The literature provides evidence of inadequate prescribing practices by dentists. The aim of this concise review was to analyse the worldwide pattern of antibiotic prescription in endodontic infections. Comprehensive searches were conducted in MEDLINE/PubMed, Wiley Online Database, Web of Science and Scopus. The databases were searched up to 13 March 2016 for studies in which dentists used systemic antibiotics to treat endodontic lesions and which reported data on the type of antibiotic prescribed and on the diagnosis of the endodontic disease treated. The electronic and hand searches identified 69 titles, of which 25 were included in the final analysis. Amoxicillin was reported as the drug of choice for endodontic infections in most countries, and clindamycin and erythromycin were the choice for patients allergic to penicillin. Dentists worldwide prescribe antibiotics for non-indicated conditions, such as pulpitis. Antibiotics are overprescribed for the management of endodontic infections. It is necessary to improve antibiotic-prescribing habits in the treatment of endodontic infections, as well as to introduce educational initiatives to encourage the coherent and proper use of antibiotics in such conditions. © 2017 FDI World Dental Federation.

Alternatives to antibiotics: why and how

USDA-ARS?s Scientific Manuscript database

The antibiotic resistance problem is the mobilization of genes that confer resistance to medically important antibiotics into human pathogens. The acquisition of such resistance genes by pathogens prevents disease treatment, increases health care costs, and increases morbidity and mortality. As ant...

Fate and effects of veterinary antibiotics in soil.

PubMed

Jechalke, Sven; Heuer, Holger; Siemens, Jan; Amelung, Wulf; Smalla, Kornelia

2014-09-01

Large amounts of veterinary antibiotics are applied worldwide to farm animals and reach agricultural fields by manure fertilization, where they might lead to an increased abundance and transferability of antibiotic-resistance determinants. In this review we discuss recent advances, limitations, and research needs in determining the fate of veterinary antibiotics and resistant bacteria applied with manure to soil, and their effects on the structure and function of soil microbial communities in bulk soils and the rhizosphere. The increased abundance and mobilization of antibiotic-resistance genes (ARGs) might contribute to the emergence of multi-resistant human pathogens that increasingly threaten the successful antibiotic treatment of bacterial infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antibiotic-resistant fecal bacteria, antibiotics, and mercury in surface waters of Oakland County, Michigan, 2005-2006

USGS Publications Warehouse

Fogarty, Lisa R.; Duris, Joseph W.; Crowley, Suzanne L.; Hardigan, Nicole

2007-01-01

Water samples collected from 20 stream sites in Oakland and Macomb Counties, Mich., were analyzed to learn more about the occurrence of cephalosporin-resistant Escherichia coli (E. coli) and vancomycin-resistant enterococci (VRE) and the co-occurrence of antibiotics and mercury in area streams. Fecal indicator bacteria concentrations exceeded the Michigan recreational water-quality standard of 300 E. coli colony forming units (CFU) per 100 milliliters of water in 19 of 35 stream-water samples collected in Oakland County. A gene commonly associated with enterococci from humans was detected in samples from Paint Creek at Rochester and Evans Ditch at Southfield, indicating that human fecal waste is a possible source of fecal contamination at these sites. E. coli resistant to the cephalosporin antibiotics (cefoxitin and/ or ceftriaxone) were found at all sites on at least one occasion. The highest percentages of E. coli isolates resistant to cefoxitin and ceftriaxone were 71 percent (Clinton River at Auburn Hills) and 19 percent (Sashabaw Creek near Drayton Plains), respectively. Cephalosporin-resistant E. coli was detected more frequently in samples from intensively urbanized or industrialized areas than in samples from less urbanized areas. VRE were not detected in any sample collected in this study. Multiple antibiotics (azithromycin, erythromycin, ofloxacin, sulfamethoxazole, and trimethoprim) were detected in water samples from the Clinton River at Auburn Hills, and tylosin (an antibiotic used in veterinary medicine and livestock production that belongs to the macrolide group, along with erythromycin) was detected in one water sample from Paint Creek at Rochester. Concentrations of total mercury were as high as 19.8 nanograms per liter (Evans Ditch at Southfield). There was no relation among percentage of antibiotic-resistant bacteria and measured concentrations of antibiotics or mercury in the water. Genetic elements capable of exchanging multiple antibiotic

Cooperation, competition and antibiotic resistance in bacterial colonies.

PubMed

Frost, Isabel; Smith, William P J; Mitri, Sara; Millan, Alvaro San; Davit, Yohan; Osborne, James M; Pitt-Francis, Joe M; MacLean, R Craig; Foster, Kevin R

2018-06-01

Bacteria commonly live in dense and genetically diverse communities associated with surfaces. In these communities, competition for resources and space is intense, and yet we understand little of how this affects the spread of antibiotic-resistant strains. Here, we study interactions between antibiotic-resistant and susceptible strains using in vitro competition experiments in the opportunistic pathogen Pseudomonas aeruginosa and in silico simulations. Selection for intracellular resistance to streptomycin is very strong in colonies, such that resistance is favoured at very low antibiotic doses. In contrast, selection for extracellular resistance to carbenicillin is weak in colonies, and high doses of antibiotic are required to select for resistance. Manipulating the density and spatial structure of colonies reveals that this difference is partly explained by the fact that the local degradation of carbenicillin by β-lactamase-secreting cells protects neighbouring sensitive cells from carbenicillin. In addition, we discover a second unexpected effect: the inducible elongation of cells in response to carbenicillin allows sensitive cells to better compete for the rapidly growing colony edge. These combined effects mean that antibiotic treatment can select against antibiotic-resistant strains, raising the possibility of treatment regimes that suppress sensitive strains while limiting the rise of antibiotic resistance. We argue that the detailed study of bacterial interactions will be fundamental to understanding and overcoming antibiotic resistance.

Self-defensive antibiotic-loaded layer-by-layer coatings: Imaging of localized bacterial acidification and pH-triggering of antibiotic release.

PubMed

Albright, Victoria; Zhuk, Iryna; Wang, Yuhao; Selin, Victor; van de Belt-Gritter, Betsy; Busscher, Henk J; van der Mei, Henny C; Sukhishvili, Svetlana A

2017-10-01

Self-defensive antibiotic-loaded coatings have shown promise in inhibiting growth of pathogenic bacteria adhering to biomaterial implants and devices, but direct proof that their antibacterial release is triggered by bacterially-induced acidification of the immediate environment under buffered conditions remained elusive. Here, we demonstrate that Staphylococcus aureus and Escherichia coli adhering to such coatings generate highly localized acidification, even in buffered conditions, to activate pH-triggered, self-defensive antibiotic release. To this end, we utilized chemically crosslinked layer-by-layer hydrogel coatings of poly(methacrylic acid) with a covalently attached pH-sensitive SNARF-1 fluorescent label for imaging, and unlabeled-antibiotic (gentamicin or polymyxin B) loaded coatings for antibacterial studies. Local acidification of the coatings induced by S. aureus and E. coli adhering to the coatings was demonstrated by confocal-laser-scanning-microscopy via wavelength-resolved imaging. pH-triggered antibiotic release under static, small volume conditions yielded high bacterial killing efficiencies for S. aureus and E. coli. Gentamicin-loaded films retained their antibacterial activity against S. aureus under fluid flow in buffered conditions. Antibacterial activity increased with the number of polymer layers in the films. Altogether, pH-triggered, self-defensive antibiotic-loaded coatings become activated by highly localized acidification in the immediate environment of an adhering bacterium, offering potential for clinical application with minimized side-effects. Polymeric coatings were created that are able to uptake and selectively release antibiotics upon stimulus by adhering bacteria in order to understand the fundamental mechanisms behind pH-triggered antibiotic release as a potential way to prevent biomaterial-associated infections. Through fluorescent imaging studies, this work importantly shows that adhering bacteria produce highly localized p

Antibiotics for community-acquired pneumonia in adult outpatients.

PubMed

Pakhale, Smita; Mulpuru, Sunita; Verheij, Theo J M; Kochen, Michael M; Rohde, Gernot G U; Bjerre, Lise M

2014-10-09

Lower respiratory tract infection (LRTI) is the third leading cause of death worldwide and the first leading cause of death in low-income countries. Community-acquired pneumonia (CAP) is a common condition that causes a significant disease burden for the community, particularly in children younger than five years, the elderly and immunocompromised people. Antibiotics are the standard treatment for CAP. However, increasing antibiotic use is associated with the development of bacterial resistance and side effects for the patient. Several studies have been published regarding optimal antibiotic treatment for CAP but many of these data address treatments in hospitalised patients. This is an update of our 2009 Cochrane Review and addresses antibiotic therapies for CAP in outpatient settings. To compare the efficacy and safety of different antibiotic treatments for CAP in participants older than 12 years treated in outpatient settings with respect to clinical, radiological and bacteriological outcomes. We searched CENTRAL (2014, Issue 1), MEDLINE (January 1966 to March week 3, 2014), EMBASE (January 1974 to March 2014), CINAHL (2009 to March 2014), Web of Science (2009 to March 2014) and LILACS (2009 to March 2014). We looked for randomised controlled trials (RCTs), fully published in peer-reviewed journals, of antibiotics versus placebo as well as antibiotics versus another antibiotic for the treatment of CAP in outpatient settings in participants older than 12 years of age. However, we did not find any studies of antibiotics versus placebo. Therefore, this review includes RCTs of one or more antibiotics, which report the diagnostic criteria and describe the clinical outcomes considered for inclusion in this review. Two review authors (LMB, TJMV) independently assessed study reports in the first publication. In the 2009 update, LMB performed study selection, which was checked by TJMV and MMK. In this 2014 update, two review authors (SP, SM) independently performed and

Inhaled antibiotics: the new era of personalized medicine?

PubMed

Biller, Julie A

2015-11-01

Treatment options for individuals with cystic fibrosis (CF) have improved survival significantly over the past two decades. One important treatment modality is inhaled antibiotics to treat chronic infection of the airways. This review includes those antibiotics that are currently in use, those that are in clinical trials. It also includes review of nonantibiotic antimicrobials, a growing area of investigation in CF. There are currently three inhaled antibiotics that are approved for use in patients with cystic fibrosis: tobramycin, aztreonam, and colistimethate. Tobramycin and colistimethate now are available as solution and new dry powder formulations, which are helping the treatment burden which has increased in CF. New antibiotics are in trial, although recently two did not meet primary outcomes in large clinical trials. Of particular interest is the development of nonantibiotic antimicrobials, which may allow treatment of intrinsically antibiotic resistant organisms. Inhaled antibiotics remain an important treatment option in cystic fibrosis due to chronic airway infection as a hallmark of the disease. Although there are now multiple options for treatment, improvements in this treatment class are needed to treat intrinsically resistant organisms. New formulation of antibiotics and nonantibiotic antimicrobials are being evaluated to add to our armamentarium.

Nanoengineered drug delivery systems for enhancing antibiotic therapy.

PubMed

Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala

2015-03-01

Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Educational Effectiveness, Target, and Content for Prudent Antibiotic Use

PubMed Central

Lee, Chang-Ro; Lee, Jung Hun; Kang, Lin-Woo; Jeong, Byeong Chul; Lee, Sang Hee

2015-01-01

Widespread antimicrobial use and concomitant resistance have led to a significant threat to public health. Because inappropriate use and overuse of antibiotics based on insufficient knowledge are one of the major drivers of antibiotic resistance, education about prudent antibiotic use aimed at both the prescribers and the public is important. This review investigates recent studies on the effect of interventions for promoting prudent antibiotics prescribing. Up to now, most educational efforts have been targeted to medical professionals, and many studies showed that these educational efforts are significantly effective in reducing antibiotic prescribing. Recently, the development of educational programs to reduce antibiotic use is expanding into other groups, such as the adult public and children. The investigation of the contents of educational programs for prescribers and the public demonstrates that it is important to develop effective educational programs suitable for each group. In particular, it seems now to be crucial to develop appropriate curricula for teaching medical and nonmedical (pharmacy, dentistry, nursing, veterinary medicine, and midwifery) undergraduate students about general medicine, microbial virulence, mechanism of antibiotic resistance, and judicious antibiotic prescribing. PMID:25945327

The Biogeography of Putative Microbial Antibiotic Production

PubMed Central

Bryant, Jessica A.; Charkoudian, Louise K.; Docherty, Kathryn M.; Jones, Evan; Kembel, Steven W.; Green, Jessica L.; Bohannan, Brendan J. M.

2015-01-01

Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics. PMID:26102275

Attitudes of pharmacists and physicians to antibiotic policies in hospitals.

PubMed

Adu, A; Simpson, J M; Armour, C L

1999-06-01

Antibiotic therapy in hospitals has substantial impact on patient outcome and the pharmacy drug budget. Antibiotic policies have been implemented by some hospitals to improve the quality of patient outcome and cost of antibiotic therapy. Antibiotic policies impose certain requirements on pharmacists and physicians. Pharmacists' and physicians' attitudes to and opinions about antibiotic policies are likely to affect the usefulness of such policies. To determine the attitudes of pharmacists and physicians to antibiotic policies in New South Wales (NSW) hospitals. Pharmacists and physicians in NSW public hospitals were surveyed to determine their attitudes to and opinions on antibiotic policies. A simple one-stage cluster sample of 241 pharmacists and a two-stage cluster sample of 701 physicians were obtained. Factor analysis was used to identify the attitudinal dimensions. General linear modelling was used to investigate the effects of predictor variables on outcome variables. The response rates were 91% and 77% for pharmacists and physicians, respectively. Factor analysis identified three dimensions of attitude to antibiotic policies: that they encourage rational antibiotic use; that they improve the quality of antibiotic prescribing and that they are associated with some problems. The reliability of these factors (Cronbach's alpha) ranged from 0.71 to 0.74, and was 0.90 for the overall attitude scale. Pharmacists and physicians had a positive overall attitude to antibiotic policies. Whereas physicians recognize that antibiotic policies improve the quality of prescribing, this was highly correlated with identification of problems (alpha = 0.71). In urban hospitals, pharmacists were more likely than physicians to associate antibiotics with problems. There was a positive overall attitude to hospital antibiotic policies expressed by pharmacists and physicians.

Antibiotic Resistance: A Primer and Call to Action

PubMed Central

Smith, Rachel A.; M’ikanatha, Nkuchia M.; Read, Andrew F.

2014-01-01

During the past century, discoveries of microorganisms as causes of infections and antibiotics as effective therapeutic agents have contributed to significant gains in public health in many parts of the world. Health agencies worldwide are galvanizing attention toward antibiotic resistance, which is a major threat to public health (Centers for Disease Control and Prevention [CDC], 2013; World Health Organization [WHO], 2014). Some life scientists believe that we are approaching the post-antibiotic age (Davies & Davies, 2010). The growing threat of antimicrobial resistance is fueled by complex factors with biological, behavioral and societal aspects. This primer provides an overview of antibiotic resistance and its growing burden on public health, the biological and behavioral mechanisms that increase antibiotic resistance, and examples of where health communication scholars can contribute to efforts to make our current antibiotic drugs last as long as possible. In addition, we identify compelling challenges for current communication theories and practices. PMID:25121990

Mechanisms of antibiotic resistance in enterococci

PubMed Central

Miller, William R; Munita, Jose M; Arias, Cesar A

2015-01-01

Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches. PMID:25199988

Antibiotics for acute otitis media in children.

PubMed

Venekamp, Roderick P; Sanders, Sharon L; Glasziou, Paul P; Del Mar, Chris B; Rovers, Maroeska M

2015-06-23

Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Antibiotic use for AOM varies from 56% in the Netherlands to 95% in the USA, Canada and Australia. This is an update of a Cochrane review first published in The Cochrane Library in Issue 1, 1997 and previously updated in 1999, 2005, 2009 and 2013. To assess the effects of antibiotics for children with AOM. We searched CENTRAL (2015, Issue 3), MEDLINE (1966 to April week 3, 2015), OLDMEDLINE (1958 to 1965), EMBASE (January 1990 to April 2015), Current Contents (1966 to April 2015), CINAHL (2008 to April 2015) and LILACS (2008 to April 2015). Randomised controlled trials (RCTs) comparing 1) antimicrobial drugs with placebo and 2) immediate antibiotic treatment with expectant observation (including delayed antibiotic prescribing) in children with AOM. Two review authors independently assessed trial quality and extracted data. For the review of antibiotics against placebo, 13 RCTs (3401 children and 3938 AOM episodes) from high-income countries were eligible and had generally low risk of bias. The combined results of the trials revealed that by 24 hours from the start of treatment, 60% of the children had recovered whether or not they had placebo or antibiotics. Pain was not reduced by antibiotics at 24 hours (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.78 to 1.01) but almost a third fewer had residual pain at two to three days (RR 0.70, 95% CI 0.57 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) 20). A quarter fewer had pain at four to seven days (RR 0.76, 95% CI 0.63 to 0.91; NNTB 16) and two-thirds fewer had pain at 10 to 12 days (RR 0.33, 95% CI 0.17 to 0.66; NNTB 7) compared with placebo. Antibiotics did reduce the number of children with abnormal tympanometry findings at two to four weeks (RR 0.82, 95% CI 0.74 to 0.90; NNTB 11), at six to eight weeks (RR 0.88, 95% CI 0.78 to 1.00; NNTB 16) and the number of children with tympanic

Non-antibiotic antimicrobial interventions and antimicrobial stewardship in wound care.

PubMed

Cooper, Rose; Kirketerp-Møller, Klaus

2018-06-02

Control of wound infection today relies largely on antibiotics, but the continual emergence of antibiotic-resistant microorganisms threatens a return to the pre-antibiotic era when physicians used antiseptics to prevent and manage infection. Some of those antiseptics are still used today, and others have become available. A diverse variety of non-antibiotic antimicrobial interventions are found on modern formularies. Unlike the mode of action of antibiotics, which affect specific cellular target sites of pathogens, many non-antibiotic antimicrobials affect multiple cellular target sites in a non-specific way. Although this reduces the likelihood of selecting for resistant strains of microorganisms, some have emerged and cross-resistance between antibiotics and antiseptics has been detected. With the prospect of a post-antibiotic era looming, ways to maintain and extend our antimicrobial armamentarium must be found. In this narrative review, current and emerging non-antibiotic antimicrobial strategies will be considered and the need for antimicrobial stewardship in wound care will be explained.

Prophylactic antibiotics in pediatric shunt surgery.

PubMed

Biyani, N; Grisaru-Soen, G; Steinbok, P; Sgouros, S; Constantini, S

2006-11-01

The optimal antibiotic prophylaxis for pediatric shunt-related procedures is not clear. There is much inconsistency among different medical centers. This paper summarizes and analyzes the various prophylactic antibiotic regiments used for shunt-related surgeries at different pediatric neurosurgery centers in the world. A survey questionnaire was distributed through the Pediatric Neurosurgery list-server (an e-mail-based special interest group in pediatric neurosurgery). Forty-five completed questionnaires were received, one per medical center, primarily from pediatric neurosurgeons with the following geographic breakdown: 25 from North America, 13 from Europe, and 7 from Asia and other countries. All centers routinely administered prophylactic antibiotics for shunt-related procedures. The drugs of choice were first-generation cephalosporins (23), second-generation cephalosporins (10), naficillin/oxacillin (4), vancomycin (3), clindamycin (1), amoxicillin (1), and mixed protocols in three centers. The initial drug administration ("first dose") was: in the department before transfer to operating room (5), upon arrival to operating room (11), at induction of anesthesia (13), and at initial skin incision (16). The duration of antibiotic dosage also varied: single dose (13), 24-h administration (26), 48-h administration (2), and longer than 48 h in four centers. Two general tendencies were noted, common to the majority of participating centers. There was a general trend to modify antibiotic treatment protocol in "high-risk" populations. The second common theme noted in more than half of responding centers was the use of long-term antibiotic treatment for externalized devices (such as externalized shunts, external ventricular drains or lumbar drains), usually till the device was in place.

Association of Adverse Events With Antibiotic Use in Hospitalized Patients.

PubMed

Tamma, Pranita D; Avdic, Edina; Li, David X; Dzintars, Kathryn; Cosgrove, Sara E

2017-09-01

Estimates of the incidence of overall antibiotic-associated adverse drug events (ADEs) in hospitalized patients are generally unavailable. To describe the incidence of antibiotic-associated ADEs for adult inpatients receiving systemic antibiotic therapy. Retrospective cohort of adult inpatients admitted to general medicine wards at an academic medical center. At least 24 hours of any parenteral or oral antibiotic therapy. Medical records of 1488 patients were examined for 30 days after antibiotic initiation for the development of the following antibiotic-associated ADEs: gastrointestinal, dermatologic, musculoskeletal, hematologic, hepatobiliary, renal, cardiac, and neurologic; and 90 days for the development of Clostridium difficile infection or incident multidrug-resistant organism infection, based on adjudication by 2 infectious diseases trained clinicians. In 1488 patients, the median age was 59 years (interquartile range, 49-69 years), and 758 (51%) participants were female. A total of 298 (20%) patients experienced at least 1 antibiotic-associated ADE. Furthermore, 56 (20%) non-clinically indicated antibiotic regimens were associated with an ADE, including 7 cases of C difficile infection. Every additional 10 days of antibiotic therapy conferred a 3% increased risk of an ADE. The most common ADEs were gastrointestinal, renal, and hematologic abnormalities, accounting for 78 (42%), 45 (24%), and 28 (15%) 30-day ADEs, respectively. Notable differences were identified between the incidence of ADEs associated with specific antibiotics. Although antibiotics may play a critical role when used appropriately, our findings underscore the importance of judicious antibiotic prescribing to reduce the harm that can result from antibiotic-associated ADEs.

Evaluation of empiric antibiotic de-escalation in febrile neutropenia.

PubMed

Kroll, Amanda L; Corrigan, Patricia A; Patel, Shejal; Hawks, Kelly G

2016-10-01

Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated guideline on the use of antimicrobial agents in neutropenic patients with cancer indicates that patients who have completed an appropriate treatment course of broad-spectrum antibiotics, with resolution of signs and symptoms of infection but persistent neutropenia, can be de-escalated to oral fluoroquinolone prophylaxis until ANC recovery. The primary objective of this retrospective investigation was to evaluate the safety and efficacy of de-escalating broad-spectrum antibiotics in patients remaining neutropenic after at least 14 days of empiric broadspectrum antibiotics for febrile neutropenia compared to patients continuing broad-spectrum antibiotics until ANC recovery. There were 16 patients (61.5%) in the comparator group who met the primary endpoint of remaining afebrile and without escalation of antibiotics for at least 72 hours after 14 days of broad-spectrum antibiotics and 21 patients (80.7%) in the de-escalation group who met the primary endpoint of remaining afebrile and without reinitiation of broad-spectrum antibiotics for at least 72 hours after de-escalation to levofloxacin therapy (p = 0.11). Mean total duration of broad-spectrum antibiotic therapy was 23.5 ± 1.5 days in the comparator group versus 22.2 ± 1.43 days in the de-escalation group (p = 0.39). Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications. © The Author(s) 2015.

Pattern of Antibiotic Prescription among Dentists in Iran

PubMed Central

Kakoei, Shahla; Raoof, Maryam; Baghaei, Fahimeh; Adhami, Shahrzad

2007-01-01

INTRODUCTION: This study examines the antibiotic prescription in dentists participated in 9th Congress of Iranian Association of Endodontists in Esfahan/2006. MATERIALS AND METHODS: A questionnaire for this cross sectional study was designed for evaluating the patterns of antibiotic prescription. It included some demographic information, clinical signs, and conditions in need for antibiotic and prophylactic prescription and their choices. Data was analyzed using Pearson’s Chi-square test. RESULTS: High percentage of responders prescribe antibiotic for fever (78.2%) and diffuse swelling (85.1%). However, some situations such as acute pulpitis, chronic periapical lesions and marginal gingivitis were irrationally prescribed. CONCLUSION: This study showed a fairly good pattern of antibiotic prescription but it was far from ideal. PMID:24348653

Microfluidics for Antibiotic Susceptibility and Toxicity Testing

PubMed Central

Dai, Jing; Hamon, Morgan; Jambovane, Sachin

2016-01-01

The recent emergence of antimicrobial resistance has become a major concern for worldwide policy makers as very few new antibiotics have been developed in the last twenty-five years. To prevent the death of millions of people worldwide, there is an urgent need for a cheap, fast and accurate set of tools and techniques that can help to discover and develop new antimicrobial drugs. In the past decade, microfluidic platforms have emerged as potential systems for conducting pharmacological studies. Recent studies have demonstrated that microfluidic platforms can perform rapid antibiotic susceptibility tests to evaluate antimicrobial drugs’ efficacy. In addition, the development of cell-on-a-chip and organ-on-a-chip platforms have enabled the early drug testing, providing more accurate insights into conventional cell cultures on the drug pharmacokinetics and toxicity, at the early and cheaper stage of drug development, i.e., prior to animal and human testing. In this review, we focus on the recent developments of microfluidic platforms for rapid antibiotics susceptibility testing, investigating bacterial persistence and non-growing but metabolically active (NGMA) bacteria, evaluating antibiotic effectiveness on biofilms and combinatorial effect of antibiotics, as well as microfluidic platforms that can be used for in vitro antibiotic toxicity testing. PMID:28952587

Antibiotic-Resistant Bacteria: There is Hope.

ERIC Educational Resources Information Center

Offner, Susan

1998-01-01

Argues that reduction in the use of antibiotics would enable antibiotic-sensitive bacteria to flourish. Presents an activity designed to show students how a small, seemingly unimportant difference in doubling time can, over a period of time, make an enormous difference in population size. (DDR)

Selective advantage of resistant strains at trace levels of antibiotics: a simple and ultrasensitive color test for detection of antibiotics and genotoxic agents.

PubMed

Liu, Anne; Fong, Amie; Becket, Elinne; Yuan, Jessica; Tamae, Cindy; Medrano, Leah; Maiz, Maria; Wahba, Christine; Lee, Catherine; Lee, Kim; Tran, Katherine P; Yang, Hanjing; Hoffman, Robert M; Salih, Anya; Miller, Jeffrey H

2011-03-01

Many studies have examined the evolution of bacterial mutants that are resistant to specific antibiotics, and many of these focus on concentrations at and above the MIC. Here we ask for the minimum concentration at which existing resistant mutants can outgrow sensitive wild-type strains in competition experiments at antibiotic levels significantly below the MIC, and we define a minimum selective concentration (MSC) in Escherichia coli for two antibiotics, which is near 1/5 of the MIC for ciprofloxacin and 1/20 of the MIC for tetracycline. Because of the prevalence of resistant mutants already in the human microbiome, allowable levels of antibiotics to which we are exposed should be below the MSC. Since this concentration often corresponds to low or trace levels of antibiotics, it is helpful to have simple tests to detect such trace levels. We describe a simple ultrasensitive test for detecting the presence of antibiotics and genotoxic agents. The test is based on the use of chromogenic proteins as color markers and the use of single and multiple mutants of Escherichia coli that have greatly increased sensitivity to either a wide range of antibiotics or specific antibiotics, antibiotic families, and genotoxic agents. This test can detect ciprofloxacin at 1/75 of the MIC.

Access to point-of-care tests reduces the prescription of antibiotics among antibiotic-requesting subjects with respiratory tract infections.

PubMed

Llor, Carl; Bjerrum, Lars; Munck, Anders; Cots, Josep M; Hernández, Silvia; Moragas, Ana

2014-12-01

General practitioners (GPs) often feel uncomfortable when patients request an antibiotic when there is likely little benefit. This study evaluates the effect of access to point-of-care tests on decreasing the prescription of antibiotics in respiratory tract infections in subjects who explicitly requested an antibiotic prescription. Spanish GPs registered all cases of respiratory tract infections over a 3-week period before and after an intervention undertaken in 2008 and 2009. Patients with acute sinusitis, pneumonia, and exacerbations of COPD were excluded. Two types of interventions were performed: the full intervention group received prescriber feedback with discussion of the results of the first registry, courses for GPs, guidelines, patient information leaflets, workshops, and access to point-of-care tests (rapid streptococcal antigen detection test and C-reactive protein test); and the partial intervention group underwent all of the above interventions except for the workshop and access to point-of-care tests. A total of 210 GPs were assigned to the full intervention group and 71 to the partial intervention group. A total of 25,479 subjects with respiratory tract infections were included, of whom 344 (1.4%) requested antibiotic prescribing. Antibiotics were more frequently prescribed to subjects requesting them compared with those who did not (49.1% vs 18.5%, P < .001). In the group of GPs assigned to the partial intervention group, 53.1% of subjects requesting antibiotics received a prescription before and 60% after the intervention, without statistical differences being observed. In the group of GPs assigned to the full intervention group, the percentages were 55.1% and 36.2%, respectively, with a difference of 18.9% (95% CI: 6.4%-30.6%, P < .05). Access to point-of-care tests reduces antibiotic use in subjects who explicitly request an antibiotic prescription. Copyright © 2014 by Daedalus Enterprises.

[Perioperative antibiotic prophylaxis in cancer surgery].

PubMed

Vilar-Compte, Diana; García-Pasquel, María José

2011-01-01

The effectiveness of perioperative antibiotic prophylaxis in reducing surgical site infections has been demonstrated. Its utility is recognized for clean-contaminated procedures and some clean surgeries. Prophylactic antibiotics are used as intended to cover the most common germs in the surgical site; first and second generation cephalosporins are the most used. For optimal prophylaxis, an antibiotic with a targeted spectrum should be administered at sufficiently high concentrations in serum, tissue, and the surgical wound during the time that the incision is open and risk of bacterial contamination. The infusion of the first dose of antimicrobial should begin within 60 min before surgical incision and should be discontinued within 24 h after the end of surgery The prolonged use of antibiotic prophylaxis leads to emergence of bacterial resistance and high costs. The principles of antimicrobial prophylaxis in cancer surgery are the same as those described for general surgery; it is recommended to follow and comply with the standard criteria. In mastectomies and clean head and neck surgery there are specific recommendations that differ from non-cancer surgery. In the case of very extensive surgeries, such as pelvic surgery or bone surgery with reconstruction, extension of antibiotics for 48-72 h should be considered.

Antibiotics for preterm rupture of membranes.

PubMed

Kenyon, Sara; Boulvain, Michel; Neilson, James P

2013-12-02

Premature birth carries substantial neonatal morbidity and mortality. Subclinical infection is associated with preterm rupture of membranes (PROM). Prophylactic maternal antibiotic therapy might lessen infectious morbidity and delay labour, but could suppress labour without treating underlying infection. To evaluate the immediate and long-term effects of administering antibiotics to women with PROM before 37 weeks, on maternal infectious morbidity, neonatal morbidity and mortality, and longer-term childhood development. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). Randomised controlled trials comparing antibiotic administration with placebo that reported clinically relevant outcomes were included as were trials of different antibiotics. Trials in which no placebo was used were included for the outcome of perinatal death alone. We extracted data from each report without blinding of either the results or the treatments that women received. We sought unpublished data from a number of authors. We included 22 trials, involving 6872 women and babies.The use of antibiotics following PROM is associated with statistically significant reductions in chorioamnionitis (average risk ratio (RR) 0.66, 95% confidence interval (CI) 0.46 to 0.96, and a reduction in the numbers of babies born within 48 hours (average RR 0.71, 95% CI 0.58 to 0.87) and seven days of randomisation (average RR 0.79, 95% CI 0.71 to 0.89). The following markers of neonatal morbidity were reduced: neonatal infection (RR 0.67, 95% CI 0.52 to 0.85), use of surfactant (RR 0.83, 95% CI 0.72 to 0.96), oxygen therapy (RR 0.88, 95% CI 0.81 to 0.96), and abnormal cerebral ultrasound scan prior to discharge from hospital (RR 0.81, 95% CI 0.68 to 0.98). Co-amoxiclav was associated with an increased risk of neonatal necrotising enterocolitis (RR 4.72, 95% CI 1.57 to 14.23).One study evaluated the children's health at seven years of age (ORACLE Children Study) and found

Antibiotics for preterm rupture of membranes.

PubMed

Kenyon, Sara; Boulvain, Michel; Neilson, James P

2010-08-04

Premature birth carries substantial neonatal morbidity and mortality. Subclinical infection is associated with preterm rupture of membranes (PROM). Prophylactic maternal antibiotic therapy might lessen infectious morbidity and delay labour, but could suppress labour without treating underlying infection. To evaluate the immediate and long-term effects of administering antibiotics to women with PROM before 37 weeks, on maternal infectious morbidity, neonatal morbidity and mortality, and longer-term childhood development. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 April 2010). Randomised controlled trials comparing antibiotic administration with placebo that reported clinically relevant outcomes were included as were trials of different antibiotics. Trials in which no placebo was used were included for the outcome of perinatal death alone. We extracted data from each report without blinding of either the results or the treatments that women received. We sought unpublished data from a number of authors. We included 22 trials, involving 6800 women and babies.The use of antibiotics following PROM is associated with statistically significant reductions in chorioamnionitis (average risk ratio (RR) 0.66, 95% confidence interval (CI) 0.46 to 0.96, and a reduction in the numbers of babies born within 48 hours (average RR 0.71, 95% CI 0.58 to 0.87) and seven days of randomisation (average RR 0.79, 95% CI 0.71 to 0.89). The following markers of neonatal morbidity were reduced: neonatal infection (RR 0.67, 95% CI 0.52 to 0.85), use of surfactant (RR 0.83, 95% CI 0.72 to 0.96), oxygen therapy (RR 0.88, 95% CI 0.81 to 0.96), and abnormal cerebral ultrasound scan prior to discharge from hospital (RR 0.81, 95% CI 0.68 to 0.98). Co-amoxiclav was associated with an increased risk of neonatal necrotising enterocolitis (RR 4.72, 95% CI 1.57 to 14.23).One study evaluated the children's health at seven years of age (ORACLE Children Study) and found

Choice of intravenous antibiotic prophylaxis for colorectal surgery does matter.

PubMed

Deierhoi, Rhiannon J; Dawes, Lillian G; Vick, Catherine; Itani, Kamal M F; Hawn, Mary T

2013-11-01

The Surgical Care Improvement Program endorses mandatory compliance with approved intravenous prophylactic antibiotics; however, oral antibiotics are optional. We hypothesized that surgical site infection (SSI) rates may vary depending on the choice of antibiotic prophylaxis. A retrospective cohort study of elective colorectal procedures using Veterans Affairs Surgical Quality Improvement Program (VASQIP) and SSI outcomes data was linked to the Office of Informatics and Analytics (OIA) and Pharmacy Benefits Management (PBM) antibiotic data from 2005 to 2009. Surgical site infection rates by type of IV antibiotic agent alone (IV) or in combination with oral antibiotic (IV + OA) were determined. Generalized estimating equations were used to examine the association between type of antibiotic prophylaxis and SSI for the entire cohort and stratified by use of oral antibiotics. After 5,750 elective colorectal procedures, 709 SSIs (12.3%) developed within 30 days. Oral antibiotic + IV (n = 2,426) had a lower SSI rate than IV alone (n = 3,324) (6.3% vs 16.7%, p < 0.0001). There was a significant difference in the SSI rate based on type of preoperative IV antibiotic given (p ≤ 0.0001). Generalized estimating equations adjusting for significant covariates of age, body mass index, procedure work relative value units, and operation duration demonstrated an independent protective effect of oral antibiotics (odds ratio [OR] 0.37, 95% CI 0.29 to 0.46), as well as increased rates of SSI associated with ampicillin/sulbactam (OR 2.21, 95% CI 1.37 to 3.56) and second generation cephalosporins (cefoxitin, OR 2.50, 95% CI 1.83 to 3.42; cefotetan, OR 2.70, 95% CI 1.72 to 4.22) when compared with first generation cephalosporin/metronidazole. The choice of IV antibiotic was related to the SSI rate; however, oral antibiotics were associated with reduced SSI rate for every antibiotic class. Published by Elsevier Inc.

Allergy to antibiotics in children: an overestimated problem.

PubMed

Esposito, Susanna; Castellazzi, Luca; Tagliabue, Claudia; Principi, Nicola

2016-10-01

Antibiotics are the most prescribed drugs for children, and a relevant number of prescriptions are associated with the emergence of adverse events. Allergic reactions are the most frequently reported adverse events, with an incidence of up to 10% of all prescriptions. However, literature analysis has shown that allergy to antibiotics is generally overdiagnosed in children because in most cases the diagnosis is based only on the clinical history without a full allergy work-up. Consequently, children are often improperly deprived of narrow-spectrum antibiotics because of a suspected allergy to these drugs. β-Lactams, mainly penicillins, are more frequently involved as a cause of allergy to antibiotics, although allergic problems are reported for most of the antibiotic classes. Accurate diagnosis is essential for a precise definition of determination of allergy to a given drug. Diagnosis has to be based on history, laboratory tests and, when possible, on in vitro and drug provocation tests. Unfortunately, the allergological work-up is well structured only for β-lactam antibiotics, whereas for non-β-lactams few studies are available, with very limited experience in children. The main aim of this paper is to discuss the real relevance of allergy to antibiotics in children in order to provide physicians with the knowledge needed to establish an appropriate diagnostic allergy work-up and to make better use of antibiotic therapy. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Silver enhances antibiotic activity against gram-negative bacteria.

PubMed

Morones-Ramirez, J Ruben; Winkler, Jonathan A; Spina, Catherine S; Collins, James J

2013-06-19

A declining pipeline of clinically useful antibiotics has made it imperative to develop more effective antimicrobial therapies, particularly against difficult-to-treat Gram-negative pathogens. Silver has been used as an antimicrobial since antiquity, yet its mechanism of action remains unclear. We show that silver disrupts multiple bacterial cellular processes, including disulfide bond formation, metabolism, and iron homeostasis. These changes lead to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria that can potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as restore antibiotic susceptibility to a resistant bacterial strain. We show both in vitro and in a mouse model of urinary tract infection that the ability of silver to induce oxidative stress can be harnessed to potentiate antibiotic activity. Additionally, we demonstrate in vitro and in two different mouse models of peritonitis that silver sensitizes Gram-negative bacteria to the Gram-positive-specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. Finally, we used silver and antibiotic combinations in vitro to eradicate bacterial persister cells, and show both in vitro and in a mouse biofilm infection model that silver can enhance antibacterial action against bacteria that produce biofilms. This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.

Antibiotic treatment of acute respiratory infections in acute care settings.

PubMed

Gonzales, Ralph; Camargo, Carlos A; MacKenzie, Thomas; Kersey, Ayanna S; Maselli, Judith; Levin, Sara K; McCulloch, Charles E; Metlay, Joshua P

2006-03-01

To examine the patterns of antibiotic use for acute respiratory tract infections (ARIs) in acute care settings. Chart reviews were performed retrospectively on a random sample of adult ARI visits to seven Veterans Affairs (VA) and seven non-VA emergency departments (EDs) for the period of November 2003 to February 2004. Visits were limited to those discharged to home and those with primary diagnoses of antibiotic-responsive (pneumonia, acute exacerbation of chronic bronchitis, pharyngitis, sinusitis) and antibiotic-nonresponsive conditions (acute bronchitis, nonspecific upper respiratory tract infection [URI]). Results are expressed as adjusted odds ratios with 95% confidence intervals. Of 2,270 ARI visits, 62% were for antibiotic-nonresponsive diagnoses. Seventy-two percent of acute bronchitis and 38% of URI visits were treated with antibiotics (p < 0.001). Stratified analyses show that antibiotic prescription rates were similar among attending-only and housestaff-associated visits for antibiotic-responsive diagnoses (p = 0.11), and acute bronchitis (76% vs. 59%; p = 0.31). However, the antibiotic prescription rate for URIs was greater for attending-only visits compared with housestaff-associated visits (48% vs. 15%; p = 0.01). Antibiotic prescription rates for total ARIs varied between sites, ranging from 42% to 89%. Patient age, gender, race and ethnicity, smoking status, comorbidities, and clinical setting (VA vs. non-VA) were not independently associated with antibiotic prescribing. Acute care settings are important targets for reducing inappropriate antibiotic prescribing. The mechanisms accounting for lower antibiotic prescription rates observed with housestaff-associated visits merit further study.

Surface modeling of soil antibiotics.

PubMed

Shi, Wen-jiao; Yue, Tian-xiang; Du, Zheng-ping; Wang, Zong; Li, Xue-wen

2016-02-01

Large numbers of livestock and poultry feces are continuously applied into soils in intensive vegetable cultivation areas, and then some veterinary antibiotics are persistent existed in soils and cause health risk. For the spatial heterogeneity of antibiotic residues, developing a suitable technique to interpolate soil antibiotic residues is still a challenge. In this study, we developed an effective interpolator, high accuracy surface modeling (HASM) combined vegetable types, to predict the spatial patterns of soil antibiotics, using 100 surface soil samples collected from an intensive vegetable cultivation area located in east of China, and the fluoroquinolones (FQs), including ciprofloxacin (CFX), enrofloxacin (EFX) and norfloxacin (NFX), were analyzed as the target antibiotics. The results show that vegetable type is an effective factor to be combined to improve the interpolator performance. HASM achieves less mean absolute errors (MAEs) and root mean square errors (RMSEs) for total FQs (NFX+CFX+EFX), NFX, CFX and EFX than kriging with external drift (KED), stratified kriging (StK), ordinary kriging (OK) and inverse distance weighting (IDW). The MAE of HASM for FQs is 55.1 μg/kg, and the MAEs of KED, StK, OK and IDW are 99.0 μg/kg, 102.8 μg/kg, 106.3 μg/kg and 108.7 μg/kg, respectively. Further, RMSE simulated by HASM for FQs (CFX, EFX and NFX) are 106.2 μg/kg (88.6 μg/kg, 20.4 μg/kg and 39.2 μg/kg), and less 30% (27%, 22% and 36%), 33% (27%, 27% and 43%), 38% (34%, 23% and 41%) and 42% (32%, 35% and 51%) than the ones by KED, StK, OK and IDW, respectively. HASM also provides better maps with more details and more consistent maximum and minimum values of soil antibiotics compared with the measured data. The better performance can be concluded that HASM takes the vegetable type information as global approximate information, and takes local sampling data as its optimum control constraints. Copyright © 2015 Elsevier B.V. All rights reserved.

Antibiotic dosing in critically ill patients receiving CRRT: underdosing is overprevalent.

PubMed

Lewis, Susan J; Mueller, Bruce A

2014-01-01

Published CRRT drug dosing algorithms and other dosing guidelines appear to result in underdosed antibiotics, leading to failure to attain pharmacodynamic targets. High mortality rates persist with inadequate antibiotic therapy as the most important risk factor for death. Reasons for unintended antibiotic underdosing in patients receiving CRRT are many. Underdosing may result from lack of the recognition that better hepatic function in AKI patients yields higher nonrenal antibiotic clearance compared to ESRD patients. Other factors include the variability in body size and fluid composition of patients, the serious consequence of delayed achievement of antibiotic pharmacodynamic targets in septic patients, potential subtherapeutic antibiotic concentrations at the infection site, and the influence of RRT intensity on antibiotic concentrations. Too often, clinicians weigh the benefits of overcautious antibiotic dosing to avoid antibiotic toxicity too heavily against the benefits of rapid attainment of therapeutic antibiotic concentrations in critically ill patients receiving CRRT. We urge clinicians to prescribe antibiotics aggressively for these vulnerable patients. © 2014 Wiley Periodicals, Inc.

Next-generation approaches to understand and combat the antibiotic resistome

PubMed Central

Crofts, Terence S.; Gasparrini, Andrew J.; Dantas, Gautam

2017-01-01

Antibiotic resistance is a natural feature of diverse microbial ecosystems. Although recent studies of the antibiotic resistome have highlighted barriers to the horizontal transfer of antibiotic resistance genes between habitats, the rapid global spread of genes that confer resistance to carbapenem, colistin and quinolone antibiotics illustrates the dire clinical and societal consequences of such events. Over time, the study of antibiotic resistance has grown from focusing on single pathogenic organisms in axenic culture to studying antibiotic resistance in pathogenic, commensal and environmental bacteria at the level of microbial communities. As the study of antibiotic resistance advances, it is important to incorporate this comprehensive approach to better inform global antibiotic resistance surveillance and antibiotic development. It is increasingly becoming apparent that although not all resistance genes are likely to geographically and phylogenetically disseminate, the threat presented by those that are is serious and warrants an interdisciplinary research focus. In this Review, we highlight seminal work in the resistome field, discuss recent advances in the studies of resistomes, and propose a resistome paradigm that can pave the way for the improved proactive identification and mitigation of emerging antibiotic resistance threats. PMID:28392565

Next-generation approaches to understand and combat the antibiotic resistome.

PubMed

Crofts, Terence S; Gasparrini, Andrew J; Dantas, Gautam

2017-07-01

Antibiotic resistance is a natural feature of diverse microbial ecosystems. Although recent studies of the antibiotic resistome have highlighted barriers to the horizontal transfer of antibiotic resistance genes between habitats, the rapid global spread of genes that confer resistance to carbapenem, colistin and quinolone antibiotics illustrates the dire clinical and societal consequences of such events. Over time, the study of antibiotic resistance has grown from focusing on single pathogenic organisms in axenic culture to studying antibiotic resistance in pathogenic, commensal and environmental bacteria at the level of microbial communities. As the study of antibiotic resistance advances, it is important to incorporate this comprehensive approach to better inform global antibiotic resistance surveillance and antibiotic development. It is increasingly becoming apparent that although not all resistance genes are likely to geographically and phylogenetically disseminate, the threat presented by those that are is serious and warrants an interdisciplinary research focus. In this Review, we highlight seminal work in the resistome field, discuss recent advances in the studies of resistomes, and propose a resistome paradigm that can pave the way for the improved proactive identification and mitigation of emerging antibiotic resistance threats.

Chitin Oligosaccharide (COS) Reduces Antibiotics Dose and Prevents Antibiotics-Caused Side Effects in Adolescent Idiopathic Scoliosis (AIS) Patients with Spinal Fusion Surgery.

PubMed

Qu, Yang; Xu, Jinyu; Zhou, Haohan; Dong, Rongpeng; Kang, Mingyang; Zhao, Jianwu

2017-03-14

Antibiotics are always considered for surgical site infection (SSI) in adolescent idiopathic scoliosis (AIS) surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide (COS) has anti-inflammation and anti-bacteria functions. The effects of COS on surgical infection in AIS surgery were investigated. A total of 312 AIS patients were evenly and randomly assigned into control group (CG, each patient took one-gram alternative Azithromycin/Erythromycin/Cloxacillin/Aztreonam/Ceftazidime or combined daily), experiment group (EG, each patient took 20 mg COS and half-dose antibiotics daily), and placebo group (PG, each patient took 20 mg placebo and half-dose antibiotics daily). The average follow-up was one month, and infection severity and side effects were analyzed. The effects of COS on isolated pathogens were analyzed. SSI rates were 2%, 3% and 8% for spine wounds and 1%, 2% and 7% for iliac wound in CG, EG and PG ( p < 0.05), respectively. COS reduces the side effects caused by antibiotics ( p < 0.05). COS improved biochemical indexes and reduced the levels of interleukin (IL)-6 and tumor necrosis factor (TNF) alpha. COS reduced the antibiotics dose and antibiotics-caused side effects in AIS patients with spinal fusion surgery by improving antioxidant and anti-inflammatory activities. COS should be developed as potential adjuvant for antibiotics therapies.

Antibiotic-resistant genes and antibiotic-resistant bacteria in the effluent of urban residential areas, hospitals, and a municipal wastewater treatment plant system.

PubMed

Li, Jianan; Cheng, Weixiao; Xu, Like; Strong, P J; Chen, Hong

2015-03-01

In this study, we determined the abundance of 8 antibiotics (3 tetracyclines, 4 sulfonamides, and 1 trimethoprim), 12 antibiotic-resistant genes (10 tet, 2 sul), 4 antibiotic-resistant bacteria (tetracycline, sulfamethoxazole, and combined resistance), and class 1 integron integrase gene (intI1) in the effluent of residential areas, hospitals, and municipal wastewater treatment plant (WWTP) systems. The concentrations of total/individual targets (antibiotics, genes, and bacteria) varied remarkably among different samples, but the hospital samples generally had a lower abundance than the residential area samples. The WWTP demonstrated removal efficiencies of 50.8% tetracyclines, 66.8% sulfonamides, 0.5 logs to 2.5 logs tet genes, and less than 1 log of sul and intI1 genes, as well as 0.5 log to 1 log removal for target bacteria. Except for the total tetracycline concentration and the proportion of tetracycline-resistant bacteria (R (2) = 0.330, P < 0.05), there was no significant correlation between antibiotics and the corresponding resistant bacteria (P > 0.05). In contrast, various relationships were identified between antibiotics and antibiotic resistance genes (P < 0.05). Tet (A) and tet (B) displayed noticeable relationships with both tetracycline and combined antibiotic-resistant bacteria (P < 0.01).

Antibiotic prophylaxis in cirrhosis: Good and bad.

PubMed

Fernández, Javier; Tandon, Puneeta; Mensa, Jose; Garcia-Tsao, Guadalupe

2016-06-01

Patients with cirrhosis, particularly those with decompensated cirrhosis, are at increased risk of bacterial infections that may further precipitate other liver decompensations including acute-on-chronic liver failure. Infections constitute the main cause of death in patients with advanced cirrhosis, and strategies to prevent them are essential. The main current strategy is the use of prophylactic antibiotics targeted at specific subpopulations at high risk of infection: prior episode of spontaneous bacterial peritonitis, upper gastrointestinal bleeding, and low-protein ascites with associated poor liver function. Antibiotic prophylaxis effectively prevents not only the development of bacterial infections in all these indications but also further decompensation (variceal bleeding, hepatorenal syndrome) and improves survival. However, antibiotic prophylaxis is also associated with a clinically relevant and increasing drawback, the development of infections due to multidrug-resistant organisms. Several strategies have been suggested to balance the risks and benefits of antibiotic prophylaxis. Antibiotic stewardship principles such as the restriction of antibiotic prophylaxis to subpopulations at a very high risk for infection, the avoidance of antibiotic overuse, and early deescalation policies are key to achieve this balance; nonantibiotic prophylactic measures such as probiotics, prokinetics, bile acids, statins, and hematopoietic growth factors could also contribute to ameliorate the development and spread of multidrug-resistant bacteria in cirrhosis. (Hepatology 2016;63:2019-2031). © 2015 by the American Association for the Study of Liver Diseases. This article has been contributed to by U.S. government employees, and their contribution is in the public domain in the U.S.A.

Insight into effects of antibiotics on reactor performance and evolutions of antibiotic resistance genes and microbial community in a membrane reactor.

PubMed

Wen, Qinxue; Yang, Lian; Zhao, Yaqi; Huang, Long; Chen, Zhiqiang

2018-04-01

A lab-scale anoxic/oxic-membrane bioreactor was designed to treat antibiotics containing wastewater at different antibiotics concentrations (0.5 mg/L, 1 mg/L and 3 mg/L of each antibiotic). Overall COD and NH 4 + N removal (more than 90%) were not affected during the exposure to antibiotics and good TN removal was also achieved, while TP removal was significantly affected. The maximum removal efficiency of penicillin and chlorotetracycline reached 97.15% and 96.10% respectively due to strong hydrolysis, and sulfamethoxazole reached 90.07% by biodegradation. However, 63.87% of norfloxacin maximum removal efficiency was achieved mainly by sorption. The system had good ability to reduce ARGs, peaking to more than 4 orders of magnitude, which mainly depended on the biomass retaining of the membrane module. Antibiotics concentration influenced the evolution of ARGs and bacterial communities in the reactor. This research provides great implication to reduce ARGs and antibiotics in antibiotics containing wastewater using A/O-MBR. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antibiotic-induced population fluctuations and stochastic clearance of bacteria

PubMed Central

Le, Dai; Şimşek, Emrah; Chaudhry, Waqas

2018-01-01

Effective antibiotic use that minimizes treatment failures remains a challenge. A better understanding of how bacterial populations respond to antibiotics is necessary. Previous studies of large bacterial populations established the deterministic framework of pharmacodynamics. Here, characterizing the dynamics of population extinction, we demonstrated the stochastic nature of eradicating bacteria with antibiotics. Antibiotics known to kill bacteria (bactericidal) induced population fluctuations. Thus, at high antibiotic concentrations, the dynamics of bacterial clearance were heterogeneous. At low concentrations, clearance still occurred with a non-zero probability. These striking outcomes of population fluctuations were well captured by our probabilistic model. Our model further suggested a strategy to facilitate eradication by increasing extinction probability. We experimentally tested this prediction for antibiotic-susceptible and clinically-isolated resistant bacteria. This new knowledge exposes fundamental limits in our ability to predict bacterial eradication. Additionally, it demonstrates the potential of using antibiotic concentrations that were previously deemed inefficacious to eradicate bacteria. PMID:29508699

Reported antibiotic use in 90 swine farms in Alberta

PubMed Central

Reid-Smith, Richard; Deckert, Anne E.; Dewey, Catherine E.; McEwen, Scott A.

2006-01-01

Abstract Antibiotic use was described using a convenience sample of 90 Alberta swine farms representing approximately 25% of the Alberta market swine production. Data on the use of antibiotics were collected through an on-farm interview questionnaire. The vast majority of antibiotics were used in feed. The chlortetracycline/sulfamethazine/penicillin combination and tylosin were the most frequently used in-feed antibiotics in weaners and growers/finishers, respectively. The use of antibiotics through water was reported mostly occasionally in all categories. The use of injectable antibiotics was reported mostly in sick pigs. Penicillin was the most common in-water and injectable antibiotic in all categories. The apparent low frequency of critically important antimicrobials for use in humans (quinolones and 3rd generation cephalosporins) is an encouraging finding from a public health perspective. The widespread and frequently reported use of penicillin and tetracycline are of public health concern considering that both antimicrobials are also used for therapeutic purposes in human medicine. PMID:16734370

Antibiotic-loaded biomaterials and the risks for the spread of antibiotic resistance following their prophylactic and therapeutic clinical use.

PubMed

Campoccia, Davide; Montanaro, Lucio; Speziale, Pietro; Arciola, Carla Renata

2010-09-01

Antibiotic-loaded biomaterials are currently part of standard medical procedures for both local treatment and prevention of implant infections. The achievement of local delivery of significant quantities of active drugs directly at the site of infection, bypassing or reducing the risks of systemic effects, represents a strong point in favor of this approach. When the aim is to resolve an existing infection, controlled local release of antibiotics can be properly targeted based on the characteristics of the bacterial isolate obtained from the infection site. Under these circumstances the choice of the antibiotic is rational and this local administration route offers new unprecedented possibilities for an efficacious in situ treatment, avoiding the adverse effects of conventional systemic chemotherapies. Although the idea of self sterilizing implants is appealing, controversial is the use of antibiotic-loaded biomaterials in uninfected tissues to prevent implant infections. Systems designed for prolonged release of prophylactic inhibitory or subinhibitory amounts of antibiotics, in absence of strict harmonized guidelines, raise concerns for their still weakly proved efficacy but, even more, for their possible contribution to enhancing biofilm formation and selecting resistant mutants. This consideration holds especially true if the antibiotic-loaded represents the first-line treatment against multiresistant strains. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Impact of Rapid Susceptibility Testing and Antibiotic Selection Strategy on the Emergence and Spread of Antibiotic Resistance in Gonorrhea

PubMed Central

Tuite, Ashleigh R; Gift, Thomas L; Chesson, Harrell W; Hsu, Katherine; Salomon, Joshua A; Grad, Yonatan H

2017-01-01

Abstract Background Increasing antibiotic resistance limits treatment options for gonorrhea. We examined the impact of a hypothetical point-of-care (POC) test reporting antibiotic susceptibility profiles on slowing resistance spread. Methods A mathematical model describing gonorrhea transmission incorporated resistance emergence probabilities and fitness costs associated with resistance based on characteristics of ciprofloxacin (A), azithromycin (B), and ceftriaxone (C). We evaluated time to 1% and 5% prevalence of resistant strains among all isolates with the following: (1) empiric treatment (B and C), and treatment guided by POC tests determining susceptibility to (2) A only and (3) all 3 antibiotics. Results Continued empiric treatment without POC testing was projected to result in >5% of isolates being resistant to both B and C within 15 years. Use of either POC test in 10% of identified cases delayed this by 5 years. The 3 antibiotic POC test delayed the time to reach 1% prevalence of triply-resistant strains by 6 years, whereas the A-only test resulted in no delay. Results were less sensitive to assumptions about fitness costs and test characteristics with increasing test uptake. Conclusions Rapid diagnostics reporting antibiotic susceptibility may extend the usefulness of existing antibiotics for gonorrhea treatment, but ongoing monitoring of resistance patterns will be critical. PMID:28968710

Antibiotic susceptibility profiles for mastitis treatment.

PubMed

Hinckley, L S; Benson, R H; Post, J E; DeCloux, J C

1985-10-01

Susceptibility tests were performed on milk samples representing prevalent mastitis infections in certain herds. Susceptibility patterns of the same bacterial species from several mastitis infections in the same herd were consistent. The herd antibiotic susceptibility profiles were used as a basis for selecting antibiotics for treatment of all such mastitis cases in that herd. A high degree of correlation was seen between the susceptibility test results and treatment results. Susceptibility patterns of the same bacterial species from mastitis infections in different herds varied greatly, which indicated that any one antibiotic would not work equally well against the same bacterial infection in every herd. Therefore, treatment should be selected on the basis of susceptibility test results. When both Streptococcus and Staphylococcus mastitis occurred in the same herd, the susceptibility patterns for the 2 bacterial species varied widely. Therefore, for herds that experienced both streptococcal and staphylococcal mastitis, antibiotics to which both bacterial species were susceptible were used for treatment.

A Pathogen-Selective Antibiotic Minimizes Disturbance to the Microbiome

PubMed Central

Yao, Jiangwei; Carter, Robert A.; Vuagniaux, Grégoire; Barbier, Maryse; Rosch, Jason W.

2016-01-01

Broad-spectrum antibiotic therapy decimates the gut microbiome, resulting in a variety of negative health consequences. Debio 1452 is a staphylococcus-selective enoyl-acyl carrier protein reductase (FabI) inhibitor under clinical development and was used to determine whether treatment with pathogen-selective antibiotics would minimize disturbance to the microbiome. The effect of oral Debio 1452 on the microbiota of mice was compared to the effects of four commonly used broad-spectrum oral antibiotics. During the 10 days of oral Debio 1452 treatment, there was minimal disturbance to the gut bacterial abundance and composition, with only the unclassified S24-7 taxon reduced at days 6 and 10. In comparison, broad-spectrum oral antibiotics caused ∼100- to 4,000-fold decreases in gut bacterial abundance and severely altered the microbial composition. The gut bacterial abundance and composition of Debio 1452-treated mice were indistinguishable from those of untreated mice 2 days after the antibiotic treatment was stopped. In contrast, the bacterial abundance in broad-spectrum-antibiotic-treated mice took up to 7 days to recover, and the gut composition of the broad-spectrum-antibiotic-treated mice remained different from that of the control group 20 days after the cessation of antibiotic treatment. These results illustrate that a pathogen-selective approach to antibiotic development will minimize disturbance to the gut microbiome. PMID:27161626

Elimination of veterinary antibiotics and antibiotic resistance genes from swine wastewater in the vertical flow constructed wetlands.

PubMed

Liu, Lin; Liu, Chaoxiang; Zheng, Jiayu; Huang, Xu; Wang, Zhen; Liu, Yuhong; Zhu, Gefu

2013-05-01

This paper investigated the efficiency of two vertical flow constructed wetlands characterized by volcanic (CW1) and zeolite (CW2) respectively, at removing three common antibiotics (ciprofloxacin HCl, oxytetracycline HCl, and sulfamethazine) and tetracycline resistance (tet) genes (tetM, tetO, and tetW) from swine wastewater. The result indicated that the two systems could significantly reduce the wastewater antibiotics content, and elimination rates were in the following sequence: oxytetracycline HCl>ciprofloxacin HCl>sulfamethazine. The zeolite-medium system was superior to that of the volcanic-medium system vis-à-vis removal, perhaps because of the differing pH values and average pore sizes of the respective media. A higher concentration of antibiotics accumulated in the soil than in the media and vegetation, indicating that soil plays the main role in antibiotics removal from wastewater in vertical flow constructed wetlands. The characteristics of the wetland medium may also affect the antibiotic resistance gene removal capability of the system; the total absolute abundances of three tet genes and of 16S rRNA were reduced by 50% in CW1, and by almost one order of magnitude in CW2. However, the relative abundances of target tet genes tended to increase following CW1 treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synergistic Photothermal and Antibiotic Killing of Biofilm-Associated Staphylococcus aureus Using Targeted Antibiotic-Loaded Gold Nanoconstructs.

PubMed

Meeker, Daniel G; Jenkins, Samir V; Miller, Emily K; Beenken, Karen E; Loughran, Allister J; Powless, Amy; Muldoon, Timothy J; Galanzha, Ekaterina I; Zharov, Vladimir P; Smeltzer, Mark S; Chen, Jingyi

2016-04-08

Resistance to conventional antibiotics is a growing public health concern that is quickly outpacing the development of new antibiotics. This has led the Infectious Diseases Society of America (IDSA) to designate Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species as "ESKAPE pathogens" on the basis of the rapidly decreasing availability of useful antibiotics. This emphasizes the urgent need for alternative therapeutic strategies to combat infections caused by these and other bacterial pathogens. In this study, we used Staphylococcus aureus ( S. aureus ) as a proof-of-principle ESKAPE pathogen to demonstrate that an appropriate antibiotic (daptomycin) can be incorporated into polydopamine-coated gold nanocages (AuNC@PDA) and that daptomycin-loaded AuNC@PDA can be conjugated to antibodies targeting a species-specific surface protein (staphylococcal protein A; Spa) as a means of achieving selective delivery of the nanoconstructs directly to the bacterial cell surface. Targeting specificity was confirmed by demonstrating a lack of binding to mammalian cells, reduced photothermal and antibiotic killing of the Spa-negative species Staphylococcus epidermidis , and reduced killing of S. aureus in the presence of unconjugated anti-Spa antibodies. We demonstrate that laser irradiation at levels within the current safety standard for use in humans can be used to achieve both a lethal photothermal effect and controlled release of the antibiotic, thus resulting in a degree of therapeutic synergy capable of eradicating viable S. aureus cells. The system was validated using planktonic bacterial cultures of both methicillin-sensitive and methicillin-resistant S. aureus strains and subsequently shown to be effective in the context of an established biofilm, thus indicating that this approach could be used to facilitate the effective treatment of intrinsically resistant biofilm infections.

Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class

PubMed Central

Tulstrup, Monica Vera-Lise; Christensen, Ellen Gerd; Carvalho, Vera; Linninge, Caroline; Ahrné, Siv; Højberg, Ole; Licht, Tine Rask; Bahl, Martin Iain

2015-01-01

Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, as it disrupts the intricate balance between specific bacterial groups within this ecosystem, potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group) were dosed by oral gavage with either amoxicillin (AMX), cefotaxime (CTX), vancomycin (VAN), metronidazole (MTZ), or water (CON) daily for 10–11 days. Bacterial composition, alpha diversity and caecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity and an increase in the relative abundance of Proteobacteria was observed for all three antibiotics. Additionally, the relative abundance of Bifidobacteriaceae was increased in the CTX group and both Lactobacillaceae and Verrucomicrobiaceae were increased in the VAN group compared to the CON group. No changes in microbiota composition or function were observed following MTZ treatment. Intestinal permeability to 4 kDa FITC-dextran decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes were found in any treatment group. A strong correlation between the level of caecal succinate, the relative abundance of Clostridiaceae 1 family in the caecum, and the level of acute phase protein haptoglobin in blood plasma was observed. In conclusion, antibiotic-induced changes in microbiota may be linked to alterations in intestinal permeability, although the specific interactions remain to be elucidated as changes in permeability did

Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class.

PubMed

Tulstrup, Monica Vera-Lise; Christensen, Ellen Gerd; Carvalho, Vera; Linninge, Caroline; Ahrné, Siv; Højberg, Ole; Licht, Tine Rask; Bahl, Martin Iain

2015-01-01

Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, as it disrupts the intricate balance between specific bacterial groups within this ecosystem, potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group) were dosed by oral gavage with either amoxicillin (AMX), cefotaxime (CTX), vancomycin (VAN), metronidazole (MTZ), or water (CON) daily for 10-11 days. Bacterial composition, alpha diversity and caecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity and an increase in the relative abundance of Proteobacteria was observed for all three antibiotics. Additionally, the relative abundance of Bifidobacteriaceae was increased in the CTX group and both Lactobacillaceae and Verrucomicrobiaceae were increased in the VAN group compared to the CON group. No changes in microbiota composition or function were observed following MTZ treatment. Intestinal permeability to 4 kDa FITC-dextran decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes were found in any treatment group. A strong correlation between the level of caecal succinate, the relative abundance of Clostridiaceae 1 family in the caecum, and the level of acute phase protein haptoglobin in blood plasma was observed. In conclusion, antibiotic-induced changes in microbiota may be linked to alterations in intestinal permeability, although the specific interactions remain to be elucidated as changes in permeability did

Rapid optical determination of β-lactamase and antibiotic activity

PubMed Central

2014-01-01

Background The absence of rapid tests evaluating antibiotic susceptibility results in the empirical prescription of antibiotics. This can lead to treatment failures due to escalating antibiotic resistance, and also furthers the emergence of drug-resistant bacteria. This study reports a rapid optical method to detect β-lactamase and thereby assess activity of β-lactam antibiotics, which could provide an approach for targeted prescription of antibiotics. The methodology is centred on a fluorescence quenching based probe (β-LEAF – β-Lactamase Enzyme Activated Fluorophore) that mimics the structure of β-lactam antibiotics. Results The β-LEAF assay was performed for rapid determination of β-lactamase production and activity of β-lactam antibiotic (cefazolin) on a panel of Staphylococcus aureus ATCC strains and clinical isolates. Four of the clinical isolates were determined to be lactamase producers, with the capacity to inactivate cefazolin, out of the twenty-five isolates tested. These results were compared against gold standard methods, nitrocefin disk test for β-lactamase detection and disk diffusion for antibiotic susceptibility, showing results to be largely consistent. Furthermore, in the sub-set of β-lactamase producers, it was demonstrated and validated that multiple antibiotics (cefazolin, cefoxitin, cefepime) could be assessed simultaneously to predict the antibiotic that would be most active for a given bacterial isolate. Conclusions The study establishes the rapid β-LEAF assay for β-lactamase detection and prediction of antibiotic activity using S. aureus clinical isolates. Although the focus in the current study is β-lactamase-based resistance, the overall approach represents a broad diagnostic platform. In the long-term, these studies form the basis for the development of assays utilizing a broader variety of targets, pathogens and drugs. PMID:24708478

Improving shared decision-making in adolescents through antibiotic education.

PubMed

Ngadimon, I W; Islahudin, F; Mohamed Shah, N; Md Hatah, E; Makmor-Bakry, M

2017-02-01

Background Shared decision-making is vital in achieving desired drug therapy goals, especially with antibiotics, in view of the potential long-term reduction in drug resistance. However, shared decision-making is rarely practiced with adolescent patients. Objectives The aim of the study was to identify the effect antibiotic education has on willingness to engage in shared decision-making among adolescents in Malaysia. Setting Participants from secondary schools in Malaysia were enrolled with ethical approval. Method The adolescents answered a validated questionnaire, which included demographics, antibiotic knowledge, attitude towards antibiotic use, and the Control Preference Scale, which measures willingness to engage in shared decision-making. Afterwards, antibiotic education was delivered to participating students. Main outcome measure Knowledge about and attitude toward antibiotics were investigated. Results A total of 510 adolescents participated in the study. Knowledge of antibiotics significantly increased post education (pre 3.2 ± 1.8 vs. post 6.8 ± 2.1, p < 0.001), as did attitude score (pre 3.3 ± 1.7 vs. post 5.4 ± 1.9, p = 0.003). Interestingly, adolescents were less likely to be passively involved in shared decision-making post education (χ = 36.9, df = 2, p < 0.001). Adolescents who were more collaborative in shared decision-making had a significantly higher total antibiotics knowledge and attitude scores compared to those who were not collaborative (p = 0.003). Conclusion The present work demonstrates that antibiotic education improves knowledge, attitude, and willingness to engage in shared decision-making among adolescents. Antibiotic education can therefore be introduced as a strategy to reduce inappropriate antibiotic use.

Binding of Aminoglycoside Antibiotics to Filtration Materials

PubMed Central

Wagman, Gerald H.; Bailey, Janet V.; Weinstein, Marvin J.

1975-01-01

An investigation to study adsorption of gentamicin and other related aminoglycoside antibiotics to cellulose, diatomaceous earth (Celite), and Seitz filter sheets was carried out. Experiments with five aminoglycosides indicated that 30 to 100% of these antibiotics was adsorbed to cellulose depending on the ratio of antibiotic to adsorbent, and the total quantity could not be removed by acidification. Similarly, a study with gentamicin found adsorption to diatomaceous earth to be in the range of 33 to 98%. Neomycin and gentamicin were also readily adsorbed to Seitz filter sheets. The data indicate that large losses may occur during filtration of these antibiotics under certain conditions, and care should be taken to properly evaluate results during studies with these compounds in the presence of adsorbent materials. PMID:1137384

Binding of aminoglycoside antibiotics to filtration materials.

PubMed

Wagman, G H; Bailey, J V; Weinstein, M J

1975-03-01

An investigation to study adsorption of gentamicin and other related aminoglycoside antibiotics to cellulose, diatomaceous earth (Celite), and Seitz filter sheets was carried out. Experiments with five aminoglycosides indicated that 30 to 100% of these antibiotics was adsorbed to cellulose depending on the ratio of antibiotic to adsorbent, and the total quantity could not be removed by acidification. Similarly, a study with gentamicin found adsorption to diatomaceous earth to be in the range of 33 to 98%. Neomycin and gentamicin were also readily adsorbed to Seitz filter sheets. The data indicate that large losses may occur during filtration of these antibiotics under certain conditions, and care should be taken to properly evaluate results during studies with these compounds in the presence of adsorbent materials.

[Non-antibiotic prophylaxis for recurrent urinary-tract infections].

PubMed

Beerepoot, M A J; ter Riet, G; Verbon, A; Nys, S; de Reijke, T M; Geerlings, S E

2006-03-11

Urinary-tract infections (UTIs) occur frequently and hence have significant financial implications. Antibiotic prophylaxis can be considered in women with recurrent UTIs. However, frequent exposure to antibiotics can lead to antimicrobial resistance and side effects. The most important steps in the pathogenesis of UTIs are the colonisation and adherence of uropathogens. Lactobacilli impede intravaginal colonisation by competing with uropathogens. Cranberries interfere with the adherence of uropathogens to uroepithelial cells. Therefore, cranberries and lactobacilli are potential alternatives in the prophylaxis of UTIs. Randomised clinical trials comparing these compounds with long-term, low-dose antibiotics for the prevention of recurrent UTIs in women have not yet been conducted. Such a trial has recently been started in The Netherlands: the 'Non-antibiotic versus antibiotic prophylaxis for recurrent urinary-tract infections' (NAPRUTI) study.