Combat Antibiotic Resistant Bacteria Research Articles

Length of antibiotic therapy among adults hospitalized with uncomplicated community-acquired pneumonia, 2013-2020.

The 2014 US National Strategy for Combating Antibiotic-Resistant Bacteria (CARB) aimed to reduce inappropriate inpatient antibiotic use by 20% for monitored conditions, such as community-acquired pneumonia (CAP), by 2020. We evaluated annual trends in length of therapy (LOT) in adults hospitalized with uncomplicated CAP from 2013 through 2020. We conducted a retrospective cohort study among adults with a primary diagnosis of bacterial or unspecified pneumonia using International Classification of Diseases Ninth and Tenth Revision codes in MarketScan and the Centers for Medicare & Medicaid Services databases. We included patients with length of stay (LOS) of 2-10 days, discharged home with self-care, and not rehospitalized in the 3 days following discharge. We estimated inpatient LOT based on LOS from the PINC AI Healthcare Database. The total LOT was calculated by summing estimated inpatient LOT and actual postdischarge LOT. We examined trends from 2013 to 2020 in patients with total LOT >7 days, which was considered an indicator of likely excessive LOT. There were 44,976 and 400,928 uncomplicated CAP hospitalizations among patients aged 18-64 years and ≥65 years, respectively. From 2013 to 2020, the proportion of patients with total LOT >7 days decreased by 25% (68% to 51%) among patients aged 18-64 years and by 27% (68%-50%) among patients aged ≥65 years. Although likely excessive LOT for uncomplicated CAP patients decreased since 2013, the proportion of patients treated with LOT >7 days still exceeded 50% in 2020. Antibiotic stewardship programs should continue to pursue interventions to reduce likely excessive LOT for common infections.

Bacterial hyperpolarization modulated by polyoxometalates for solutions of antibiotic resistance

Developing strategies against the antibiotic resistance is a major global challenge for public health. Here, we report the synergy of the combination of Preyssler-type polyoxometalates (POMs) ([NaP5W30O110]14− or [AgP5W30O110]14−) and ribosome-targeting antibiotics for high antibacterial efficiency with low risk of antibiotic resistance. Due to their ultra-small sizes and active surface ligands, POM anions show strong affinity to bacterial cell membrane and impose hyperpolarization of the bacterial cells as well as the decrease of Mg2+ influx by blocking Mg2+ transporters, which finally lead to the structural perturbations of ribosomes and instability of bacterial structures. The bacterial growth can, therefore, be regulated by the presence of POMs: a fraction of Bacillus subtilis shifted to a ‘dormant’, slow-growing cellular state (an extended lag phase) upon the application of subinhibitory concentration of POMs. An approach to combat antibiotic resistant bacteria by applying POMs at their early growth phase followed by antibiotic exposure is validated, and its high efficiency for bacterial control is confirmed.

Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy.

SummaryCombinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and cytotoxicity. Moreover, the ILs which exhibit synergy with small-molecule antibiotics appear to be acting in a membrane permeabilizing manner. Collectively, results from these experiments demonstrate an increase in antimicrobial efficacy with specific IL + antimicrobial combinations on microbial cultures while maintaining low cytotoxicity in a mammalian cell culture model.

Potent Broad-Spectrum Antibacterial Activity of Amphiphilic Peptides against Multidrug-Resistant Bacteria.

The emergence and prevalence of multidrug-resistant (MDR) bacteria particularly Gram-negative bacteria presents a global crisis for human health. Colistin and tigecycline were recognized as the last resort of defenses against MDR Gram-negative pathogens. However, the emergence and prevalence of MCR or Tet(X)-mediated acquired drug resistance drastically impaired their clinical efficacy. It has been suggested that antimicrobial peptides might act a crucial role in combating antibiotic resistant bacteria owing to their multiple modes of action and characteristics that are not prone to developing drug resistance. Herein, we report a safe and stable tryptophan-rich amphiphilic peptide termed WRK-12 with broad-spectrum antibacterial activity against various MDR bacteria, including MRSA, colistin and tigecycline-resistant Escherichia coli. Mechanistical studies showed that WRK-12 killed resistant E. coli through permeabilizing the bacterial membrane, dissipating membrane potential and triggering the production of reactive oxygen species (ROS). Meanwhile, WRK-12 significantly inhibited the formation of an E. coli biofilm in a dose-dependent manner. These findings revealed that amphiphilic peptide WRK-12 is a promising drug candidate in the fight against MDR bacteria.

Biogenic Silver Nanoparticles Decorated with Methylene Blue Potentiated the Photodynamic Inactivation of Pseudomonas aeruginosa and Staphylococcus aureus.

The persistence of multidrug resistance among microorganisms has directed a mandate towards a hunt for the development of alternative therapeutic modalities. In this context, antimicrobial photodynamic therapy (aPDT) is sprouted as a novel strategy to mitigate biofilms and planktonic cells of pathogens. Nanoparticles (NPs) are reported with unique intrinsic and antimicrobial properties. Therefore, silver NPs (AgNPs) were investigated in this study to determine their ability to potentiate the aPDT of photosensitizer against Staphylococcus aureus and Pseudomonas aeruginosa. Biologically synthesized AgNPs were surface coated with methylene blue (MB) and studied for their aPDT against planktonic cells and biofilms of bacteria. The nano-conjugates (MB-AgNPs) were characterized for their size, shape and coated materials. MB-AgNPs showed significant phototoxicity against both forms of test bacteria and no toxicity was observed in the dark. Moreover, activity of MB-AgNPs was comparatively higher than that of the free MB, which concludes that MB-AgNPs could be an excellent alternative to combat antibiotic resistant bacteria.

Biomimetic antimicrobial material strategies for combating antibiotic resistant bacteria.

Antibiotic drugs have revolutionized the field of medicine for almost 90 years. However, continued use has led to the rise of antibiotic resistant bacteria, motivating the need for alternative treatments. Several strategies to combat this phenomenon have been investigated, with biomimetic strategies gaining significant appeal due to inherent compatibility with physiologically relevant environments. In this review, we will discuss current antimicrobial strategies and then present an overview on biomimetic antimicrobial material-based strategies for combating antibiotic resistant bacteria.

The role of the innate immune system on pulmonary infections.

Inhalation is required for respiration and life in all vertebrates. This process is not without risk, as it potentially exposes the host to environmental pathogens with every breath. This makes the upper respiratory tract one of the most common routes of infection and one of the leading causes of morbidity and mortality in the world. To combat this, the lung relies on the innate immune defenses. In contrast to the adaptive immune system, the innate immune system does not require sensitization, previous exposure or priming to attack foreign particles. In the lung, the innate immune response starts with the epithelial barrier and mucus production and is reinforced by phagocytic cells and T cells. These cells are vital for the production of cytokines, chemokines and anti-microbial peptides that are critical for clearance of infectious agents. In this review, we discuss all aspects of the innate immune response, with a special emphasis on ways to target aspects of the immune response to combat antibiotic resistant bacteria.

Harnessing snake venom phospholipases A2 to novel approaches for overcoming antibiotic resistance.

The emergence of antibiotic resistance drives an essential race against time to reveal new molecular structures capable of addressing this alarming global health problem. Snake venoms are natural catalogs of multifunctional toxins and privileged frameworks, which serve as potential templates for the inspiration of novel treatment strategies for combating antibiotic resistant bacteria. Phospholipases A2 (PLA2 s) are one of the main classes of antibacterial biomolecules, with recognized therapeutic value, found in these valuable secretions. Recently, a number of biomimetic oligopeptides based on small fragments of primary structure from PLA2 toxins has emerged as a meaningful opportunity to overcome multidrug-resistant clinical isolates. Thus, this review will highlight the biochemical and structural properties of antibacterial PLA2 s and peptides thereof, as well as their possible molecular mechanisms of action and key roles in development of effective therapeutic strategies. Chemical strategies possibly useful to convert antibacterial peptides from PLA2 s to efficient drugs will be equally addressed.

Development and Validation of a Microtiter Plate-Based Assay for Determination of Bacteriophage Host Range and Virulence.

Bacteriophages, which are the natural predators of bacteria, have re-emerged as an attractive alternative to combat antibiotic resistant bacteria. Phages are highly specific at the species and strain level and measurement of the phage host range plays an important role in utilizing the phage as antimicrobials. The most common method for phage host range determination has been to spot phage lysates on soft agar overlays and observe plaque formation. In this study, a liquid culture-based assay was developed in a 96-well microtiter plate format to measure the phage host range and virulence for a collection of 15 Salmonella phages against a panel of 20 Salmonella strains representing 11 serovars. This method was compared to a traditional spot method. The majority of the host range results from two methods were in agreement including in cases where a bacterial strain was insensitive to the phage. Each method produced a false-negative result in 19/300 (6%) of the measured phage-host combinations when compared to the other method. The spot method tended to indicate greater phage sensitivity than the microtiter assay even though direct comparisons of the response magnitude between the two methods is difficult since they operate on different mechanisms. The microtiter plate assay was able to provide data on both the phage host range and virulence in greater resolution in a high-throughput format.

Synthesis and antibacterial evaluation of novel cationic chalcone derivatives possessing broad spectrum antibacterial activity

There is an urgent need to identify new antibiotics with novel mechanisms that combat antibiotic resistant bacteria. Herein, a series of chalcone derivatives that mimic the essential properties of cationic antimicrobial peptides were designed and synthesized. Antibacterial activities against drug-sensitive bacteria, including Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Salmonella enterica, as well as clinical multiple drug resistant isolates of methicillin-resistant S. aureus (MRSA), KPC-2-producing and NDM-1-producing Carbapenem-resistant Enterobacteriaceae were evaluated. Representative compounds 5a (MIC: 1 μg/mL against S. aureus, 0.5 μg/mL against MRSA) and 5g (MIC: 0.5 μg/mL against S. aureus, 0.25 μg/mL against MRSA) showed good bactericidal activity against both Gram-positive and Gram-negative bacteria, including the drug-resistant species MRSA, KPC and NDM. These membrane-active antibacterial compounds were demonstrated to reduce the viable cell counts in bacterial biofilms effectively and do not induce the development of resistance in bacteria. Additionally, these representative molecules exhibited negligible toxicity toward mammalian cells at a suitable concentration. The combined results indicate that this series of cationic chalcone derivatives have potential therapeutic effects against bacterial infections.

Inhibitory Effect of Bacteriophages Isolated from Sewage Water in the City of Kirkuk on some Types of Human Pathogenic Bacteria

Most approaches to combat antibiotic resistant bacteria concentrate on discovering new antibiotics or modifying existing ones. However, one of the most promising alternatives is the use of bacteriophages. This study was focused on the isolation of bacteriophages that are specific to some of commonly human pathogens namely E. coli, Streptococcus pyogenes, Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella spp. and Klebsiella pneumoniae. These bacteriophages were isolated from sewages that were collected from four different locations in Kirkuk City. Apart from S. pyogenes, bacteriophages specific to all tested bacteria were successfully isolated and tested for their effectiveness by spot test. The most effective bacteriophages that were isolated from sewages and sewage water of Al-Jumhori Hospital compared to other sites. It is concluded that the sewage water of hospitals represents a perfect environment for these bacteriophages.

Antibacterial Activity of Azadirachta indica Leaf Extracts Against Some Pathogenic Standards and Clinical Bacterial Isolates

Background: Azadirachta indica A. Juss (Neem) has been used against a few diseases in traditional medicine. This study was conducted to evaluate the antibacterial activity of Neem leaves extract against some antibiotic sensitive and resistant strains of important human pathogenic bacteria. Methods: The antimicrobial activities of ethanol, methanol, and ethyl acetate extracts of Azadirachta indica A. juss leaves were evaluated against some pathogenic bacterial strains including S. aureus ATCC 6538, E. faecalis ATCC 1394, P. aeroginosa ATCC 9027, E.coli, ATCC 25922, and their clinical isolates using agar well diffusion and MTT microdilution methods. MBC was determined by subculturing from microdilution assays. Results: The results revealed that methanol extract has the strongest growth inhibitory effect on both standard and clinical isolated strains of P. aeroginosa. Ethyl acetate and ethanol extracts, showing a growth inhibitory effect on both standard and hospital isolated strains of S. aureus. In the case of E. faecalis, ethanol and methanol extracts showed the highest growth inhibitory effect against standard and clinical strains, respectively. According to the MIC index results, the methanol extract has a bactericidal activity against both standard and nosocomial strains of S. aureus and P. aeroginosa and bacteriostatic activity against nosocomial strain of E. faecalis. Ethanol extract showed bactericidal activity against both standard and nosocomial strains of E. faecalis and P. aeroginosa and bacteriostatic activity against nosocomial strain of S. aureus. Ethyl acetate extract had shown bactericidal activity against standard strains of S. aureus and P. aeroginosa and bacteriostatic against nosocomial strain of S. aureus and standard strain of E. faecalis. Conclusions: Results revealed that Neem may be a prospective therapeutic agent to combat antibiotic resistant bacteria.

Inhibitory Effect of Bacteriophages Isolated from Sewage Water in the City of Kirkuk on some Types of Human Pathogenic Bacteria

Most approaches to combat antibiotic resistant bacteria concentrate on discovering new antibiotics or modifying existing ones. However, one of the most promising alternatives is the use of bacteriophages. This study was focused on the isolation of bacteriophages that are specific to some of commonly human pathogens namely E. coli, Streptococcus pyogenes, Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella spp. and Klebsiella pneumoniae. These bacteriophages were isolated from sewages that were collected from four different locations in Kirkuk City. Apart from S. pyogenes, bacteriophages specific to all tested bacteria were successfully isolated and tested for their effectiveness by spot test. The most effective bacteriophages that were isolated from sewages and sewage water of Al-Jumhori Hospital compared to other sites. It is concluded that the sewage water of hospitals represents a perfect environment for these bacteriophages.

Low Completion and Disparities in Advance Care Planning Activities Among Older Medicare Beneficiaries

Letters Chicago; Ann Thomas, MD, MPH, Oregon Public Health Division, Portland; Teri Moser Woo, PhD, Pacific Lutheran University, Tacoma, Washington; Rachel M. Zetts, The Pew Charitable Trusts, Washington, DC. Conflict of Interest Disclosures: Dr Hersh has received funding from the CDC, the Agency for Healthcare Research and Quality, Pfizer/Joint Commission, and Merck. No other conflicts are reported. Funding/Support: This project was made possible through a partnership with the CDC Foundation. Support for this project was provided by Pew Charitable Trusts. Role of the Funder/Sponsor: The CDC participated in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The Pew Charitable Trusts participated in the interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The Pew Charitable Trusts sponsored in-person and telephone author meetings and supported some author travel to in-person meetings. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC. Additional Contributions: Tia Carter, MS, Allan Coukell, BSc Pharm, and Elizabeth Jungman, JD, MPH, of The Pew Charitable Trusts assisted in convening author meetings. They did not receive any compensation for their role in the study. 1. The White House. National action plan for combating antibiotic resistant bacteria. https://www.whitehouse.gov/sites/default/files/docs/national_action _plan_for_combating_antibotic-resistant_bacteria.pdf. Accessed August 3, 2015. 2. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 3. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105(4):259-273. 4. Piccirillo JF, Mager DE, Frisse ME, Brophy RH, Goggin A. Impact of first-line vs second-line antibiotics for the treatment of acute uncomplicated sinusitis. JAMA. 5. Capra AM, Lieu TA, Black SB, Shinefield HR, Martin KE, Klein JO. Costs of otitis media in a managed care population. Pediatr Infect Dis J. 2000;19(4): Table 1. Characteristics of Participants Participants, No. (%) a Variable Sociodemographic characteristics Age, y Sex Female Male Race/ethnicity White Black/African American Hispanic/Latino English-speaking Spanish-speaking Other Education High school diploma or less Greater than high school Annual income, b $ Health-related characteristics Self-rated health Excellent or very good Good Fair or poor Dementia c None Possible or probable dementia Low Completion and Disparities in Advance Care Planning Activities Among Older Medicare Beneficiaries Advance care planning (ACP) is an iterative process that in- cludes discussions about preferences for end-of-life (EOL) care, completion of advance directives (AD), and designation of a surrogate decision maker in a durable power of attorney for health care (DPOA). 1,2 Engagement in ACP has increased over time. 3 However, the rising tide of ACP may not have lifted all boats equally. Minorities, those with lower levels of educa- tional attainment, and the poor may not have benefited from rising rates of ACP to the same extent that white, highly edu- cated, affluent individuals have. Rates of ACP by older Lati- nos in particular are unknown. Further, we do not know if ACP uptake is greater among those in worse health and with poorer prognoses. Methods | We used data from the National Health and Aging Trends Study (NHATS), a longitudinal cohort study using a nationally representative sample of community-dwelling Medi- care beneficiaries ages 65 years and older (2011 round 1 re- sponse rate, 71%; 2012 round 2 response rate, 86%). 4 This cross- sectional analysis used a random one-third sample of 2015 d Number of chronic medical conditions None Number of ADLs requiring help e 1 or 2 (continued) participants who responded to a supplemental module on ACP fielded in 2012. This study was considered exempt by the institutional review board of the University of California, San Francisco. Outcome variables included 3 self-reported elements of ACP: (1) discussing with any individual the medical treat- ment desired if seriously ill in the future (EOL discussion), (2) having legal arrangements for a proxy to make decisions about medical care (DPOA), or (3) having written instructions about JAMA Internal Medicine December 2016 Volume 176, Number 12 (Reprinted) jamainternalmedicine.com Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jamanetwork.com/pdfaccess.ashx?url=/data/journals/intemed/935892/ by a UCSF LIBRARY User on 06/15/2017

Phage on the stage.

The resurgence of interest in bacteriophages for use in combating antibiotic resistant bacteria is coincident with an urgent call for more effective science education practices, including hands-on learning opportunities. To address this issue, a number of solutions have been proposed, including a large educational experiment, begun in 2007 by the Howard Hughes Medical Institute and currently involving over 85 colleges and universities, which has students discovering unique phages, obtaining images, and purifying phage DNA. A subset of these phage genomes is sequenced and analyzed using bioinformatics tools. Papers describing individual phage discoveries and comparative genomic studies are being published regularly. The vast majority of students in the program are in their first year of college, a critical time in capturing their interest and retaining them as science majors. This viral discovery model is being adopted and modified by a wide variety of educational institutions using a number of different bacterial hosts. In the opinion of the authors, this program and others like it represent a model accessible to virtually any undergraduate setting. And because of these programs, bacteriophage enthusiasts (academics, health professionals, biotechnology companies) can look forward to more well prepared students entering their ranks and should anticipate many more potentially useful phages discovered and characterized.

Experience of the Eliava Institute in bacteriophage therapy.

The rapid propagation of multidrug resistant bacterial strains is leading to renewed interest in bacteriophage therapy. With challenges in the treatment of bacterial infections, it is essential for people worldwide to understand how alternative approaches, such as bacteriophages, could be used to combat antibiotic resistant bacteria. The Eliava Institute of Bacteriophages, Microbiology and Virology (Tbilisi, Georgia) is arguably the most famous institution in the world focused on the isolation, study, and selection of phages active against a variety of bacterial pathogens.

Antibacterial activity of Parmelia perlata

ObjectiveTo test efficacy of Parmelia perlata (P. perlata), which is used in traditional medicine for rapid wound healing against test bacteria that cause wound infections. MethodsDifferent solvents such as methanol, ethyl acetate and acetone were used for extraction of P. perlata. The sensitivity of the test bacteria to solvent extracts of P. perlata was tested by measuring the zone of inhibition on growth media and by determining the minimal inhibitory concentration and minimal bactericidal concentration. ResultsMethanol, ethyl acetate and acetone extracts of P. perlata have shown inhibitory activity against Staphylococcus aureus (S. aureus). ConclusionsThe results of the present study indicate that P. perlata has potential antibacterial compounds against S. aureus that causes multitude of skin infections among human beings. Development of drugs from natural compounds can help us to combat antibiotic–resistant bacteria.

Photodynamic therapy using Photosens for the treatment of chronic central serous chorioretinopathy

Photodynamic therapy (PDT) and the use of cationic antimicrobial peptides (AMPs) are two very promising strategies to combat antibiotic resistant bacteria. Recently, we demonstrated that the conjugation of a porphyrin photosensitizer with Apidaecin 1b, a small peptide belonging to the Pro-Arg rich AMPs family, provides a potent antimicrobial agent with broad spectrum activity. Porphycenes are structural isomers of porphyrins with 10-fold higher absorption coefficient in the red part of the spectrum, and excellent photochemical and photodynamic properties. Therefore, in an attempt to improve the potential application of the photosensitizer—peptide conjugates, we extended our studies to a porphycene—apidaecin conjugate, in which the porhycene is linked to the N-terminus of Apidaecin. After checking that conjugation is not detrimental of the photophysical properties of the porphycene the antibacterial activity of the conjugate (hereafter G-api) was tested against Gram negative (E. coli) and Gram positive (methicillin resistant S. aureus) bacteria. The phototoxic activity against eukaryotic cells was measured to assess selectivity. In the dark G-api did not exhibit any toxicity against both E. coli and S. aureus. On the contrary, following activation with red light (36 J/cm2), G-api caused a significant (3—4 log10) reduction of both E. coli and S. aureus survival. Under the same experimental conditions porphycene plus Apidaecin, administrated together but not conjugated, did not affect the survival of both E. coli and S. aureus. The G-api conjugate therefore appears a very promising agent for the photoinactivation of both Gram positive and Gram negative bacteria.

Combating antibiotic resistance in bacteria.

Combinations of certain antibiotics select against resistant strains of bacteria. This finding may provide a strategy of combating antibiotic resistant bacteria.