ANTIMICROBIAL AGENTS

PEDIATRICS ◽  
1959 ◽  
Vol 23 (6) ◽  
pp. 1192-1198
Author(s):  
Mark H. Lepper ◽  
Harris D. Riley
Keyword(s):  
Side Effects ◽  
Infectious Diseases ◽  
Pneumococcal Pneumonia ◽  
Antimicrobial Agents ◽  
Simultaneous Administration ◽  
Streptococcal Infections ◽  
Lively Discussion ◽  
Clinical Observations ◽  
Resistant Strains ◽  
Disease Hospital

Hyperacute infections, i.e., infections which are often fatal within 24 hours from the onset of symptoms, and resistant strains of organisms, account for the vast majority of failures in the use of antibiotics. A few cases cannot be classified into either category and remain as unexplained failures. The magnitude of the problem of hyperacute infections can be judged by the fact that in a contagious disease hospital about a third of the fatalities from nontuberculous, bacterial infectious diseases occur within the first 24 hours from the onset of symptoms. Meningitis due to meningococcus or pneumococcus, or meningococcemia, are most commonly encountered in this group. In Dr. Lepper's experience, those patients who will die within 24 hours from onset of symptoms can be predicted early from clinical observations, and they command "heroic therapy." A lively discussion of the use of adrenal corticosteroids as pant of "heroic therapy" in hyperacute infections ensued. Dr. Riley pointed out that they are useful agents but have serious side effects and definite hazards. They are known to decrease the resistance of the host to infection. (The effect of cortisone on streptococcal infections in the rabbit was cited: 58 out of 66 rabbits pretreated with cortisone died; 5 of 60 control animals died.) Instances of empyema developing during treatment of pneumococcal pneumonia with both antibiotics and ACTH were described. The discussants agreed that at no time should adrenal corticosteroids be used in the treatment of infectious processes without simultaneous administration of adequate amounts of appropriate antibiotics.

scholarly journals Where Have all the Antibiotics Gone?

2006 ◽  
Vol 17 (5) ◽  
pp. 287-290 ◽  
Author(s):  
Julian Davies
Keyword(s):  
Pharmaceutical Industry ◽  
Infectious Diseases ◽  
Antimicrobial Agents ◽  
Therapeutic Agents ◽  
Microbial Evolution ◽  
Microbial Diseases ◽  
Alternative Approaches ◽  
Resistant Strains ◽  
Antibiotic Discovery ◽  
Novel Antibiotics

The discovery of antibiotics some 60 years ago was anticipated to herald the end of infectious diseases. However, microbial evolution and genetic jugglery have dispelled this notion; the constant increase in the appearance of resistant strains has not been matched by the introduction of new therapeutic agents. On the contrary, the dire need for novel antibiotics has coincided with a reduction in antibiotic discovery programs in the pharmaceutical industry. As a result, the treatment of microbial diseases has reached a point where many infections are essentially untreatable by the antimicrobial agents currently available. At the present time, numerous initiatives are being undertaken by physicians and by governments in an attempt to redress this situation. In addition, alternative approaches to antibiotics for the treatment of infectious diseases are being explored intensively.

Mechanisms involved in effects of antimicrobial peptides, bactenectins ChBac3.4, ChBac5, and mini-ChBac7.5Nb, on bacterial cells

2017 ◽  
pp. 43-50
Author(s):  
О.В. Шамова ◽  
М.С. Жаркова ◽  
П.М. Копейкин ◽  
Д.С. Орлов ◽  
Е.А. Корнева
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Innate Immunity ◽  
Infectious Diseases ◽  
Metabolic Activity ◽  
Capra Hircus ◽  
Bacterial Cells ◽  
Antibiotic Resistant ◽  
Resistant Strains

Антимикробные пептиды (АМП) системы врожденного иммунитета - соединения, играющие важную роль в патогенезе инфекционных заболеваний, так как обладают свойством инактивировать широкий спектр патогенных бактерий, обеспечивая противомикробную защиту живых организмов. В настоящее время АМП рассматриваются как потенциальные соединения-корректоры инфекционной патологии, вызываемой антибиотикорезистентными бактериями (АБР). Цель данной работы состояла в изученим механизмов антибактериального действия трех пептидов, принадлежащих к семейству бактенецинов - ChBac3.4, ChBac5 и mini-ChBac7.5Nb. Эти химически синтезированные пептиды являются аналогами природных пролин-богатых АМП, обнаруженных в лейкоцитах домашней козы Capra hircus и проявляющих высокую антимикробную активность, в том числе и в отношении грамотрицательных АБР. Методы. Минимальные ингибирующие и минимальные бактерицидные концентрации пептидов (МИК и МБК) определяли методом серийных разведений в жидкой питательной среде с последующим высевом на плотную питательную среду. Эффекты пептидов на проницаемость цитоплазматической мембраны бактерий для хромогенного маркера исследовали с использованием генетически модифицированного штамма Escherichia coli ML35p. Действие бактенецинов на метаболическую активность бактерий изучали с применением маркера резазурина. Результаты. Показано, что все исследованные пептиды проявляют высокую антимикробную активность в отношении Escherichia coli ML35p и антибиотикоустойчивых штаммов Escherichia coli ESBL и Acinetobacter baumannii in vitro, но их действие на бактериальные клетки разное. Использован комплекс методик, позволяющих наблюдать в режиме реального времени динамику действия бактенецинов в различных концентрациях (включая их МИК и МБК) на барьерную функцию цитоплазматической мембраны и на интенсивность метаболизма бактериальных клеток, что дало возможность выявить различия в характере воздействия бактенецинов, отличающихся по структуре молекулы, на исследуемые микроорганизмы. Установлено, что действие каждого из трех исследованных бактенецинов в бактерицидных концентрациях отличается по эффективности нарушения целостности бактериальных мембран и в скорости подавления метаболизма клеток. Заключение. Полученная информация дополнит существующие фундаментальные представления о механизмах действия пролин-богатых пептидов врожденного иммунитета, а также послужит основой для биотехнологических исследований, направленных на разработку на базе этих соединений новых антибиотических препаратов для коррекции инфекционных заболеваний, вызываемых АБР и являющимися причинами тяжелых внутрибольничных инфекций. Antimicrobial peptides (AMPs) of the innate immunity are compounds that play an important role in pathogenesis of infectious diseases due to their ability to inactivate a broad array of pathogenic bacteria, thereby providing anti-microbial host defense. AMPs are currently considered promising compounds for treatment of infectious diseases caused by antibiotic-resistant bacteria. The aim of this study was to investigate molecular mechanisms of the antibacterial action of three peptides from the bactenecin family, ChBac3.4, ChBac5, and mini-ChBac7.5Nb. These chemically synthesized peptides are analogues of natural proline-rich AMPs previously discovered by the authors of the present study in leukocytes of the domestic goat, Capra hircus. These peptides exhibit a high antimicrobial activity, in particular, against antibiotic-resistant gram-negative bacteria. Methods. Minimum inhibitory and minimum bactericidal concentrations of the peptides (MIC and MBC) were determined using the broth microdilution assay followed by subculturing on agar plates. Effects of the AMPs on bacterial cytoplasmic membrane permeability for a chromogenic marker were explored using a genetically modified strain, Escherichia coli ML35p. The effect of bactenecins on bacterial metabolic activity was studied using a resazurin marker. Results. All the studied peptides showed a high in vitro antimicrobial activity against Escherichia coli ML35p and antibiotic-resistant strains, Escherichia coli ESBL and Acinetobacter baumannii, but differed in features of their action on bacterial cells. The used combination of techniques allowed the real-time monitoring of effects of bactenecin at different concentrations (including their MIC and MBC) on the cell membrane barrier function and metabolic activity of bacteria. The differences in effects of these three structurally different bactenecins on the studied microorganisms implied that these peptides at bactericidal concentrations differed in their capability for disintegrating bacterial cell membranes and rate of inhibiting bacterial metabolism. Conclusion. The obtained information will supplement the existing basic concepts on mechanisms involved in effects of proline-rich peptides of the innate immunity. This information will also stimulate biotechnological research aimed at development of new antibiotics for treatment of infectious diseases, such as severe in-hospital infections, caused by antibiotic-resistant strains.

scholarly journals Arginine Is a Critical Substrate for the Pathogenesis of Pseudomonas aeruginosa in Burn Wound Infections

mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Jake Everett ◽  
Keith Turner ◽  
Qiuxian Cai ◽  
Vernita Gordon ◽  
Marvin Whiteley ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Hospital Setting ◽  
Multidrug Resistant ◽  
Burn Patients ◽  
Burn Wound ◽  
Burn Wounds ◽  
Resistant Strains ◽  
High Doses ◽  
Ubiquitous Presence

ABSTRACT Environmental conditions affect bacterial behavior and can greatly influence the course of an infection. However, the environmental cues that elicit bacterial responses in specific infection sites are relatively unknown. Pseudomonas aeruginosa is ubiquitous in nature and typically innocuous. However, it is also one of the most prevalent causes of fatal sepsis in burn wound patients. The aim of this study was to determine the impact of environmental factors, specifically the availability of arginine, on the pathogenesis of P. aeruginosa in burn wound infections. Comparison of burned versus noninjured tissue revealed that l-arginine (l-Arg) was significantly depleted in burn wounds as a consequence of elevated arginase produced by myeloid-derived suppressor cells. We also observed that l-Arg was a potent chemoattractant for P. aeruginosa, and while low concentrations of l-Arg increased P. aeruginosa’s swimming motility, high concentrations resulted in diminished swimming. Based on these observations, we tested whether the administration of exogenous l-Arg into the burn wound could attenuate the virulence of P. aeruginosa in thermally injured mice. Administration of l-Arg resulted in decreased P. aeruginosa spread and sepsis and increased animal survival. Taken together, these data demonstrate that the availability of environmental arginine greatly influences the virulence of P. aeruginosa in vivo and may represent a promising phenotype-modulating tool for future therapeutic avenues. IMPORTANCE Despite our growing understanding of the pathophysiology of burn wounds and the evolution of techniques and practices to manage infections, sepsis remains a significant medical concern for burn patients. P. aeruginosa continues to be a leader among all causes of bacteremic infections due to its tendency to cause complications in immunocompromised patients and its ubiquitous presence in the hospital setting. With the unforgiving emergence of multidrug-resistant strains, it is critical that alternative strategies to control or prevent septic infections in burn patients be developed in parallel with novel antimicrobial agents. In this study, we observed that administration of l-Arg significantly reduced bacterial spread and sepsis in burned mice infected with P. aeruginosa. Given the safety of l-Arg in high doses and its potential wound-healing benefits, this conditionally essential amino acid may represent a useful tool to modulate bacterial behavior in vivo and prevent sepsis in burn patients. IMPORTANCE Despite our growing understanding of the pathophysiology of burn wounds and the evolution of techniques and practices to manage infections, sepsis remains a significant medical concern for burn patients. P. aeruginosa continues to be a leader among all causes of bacteremic infections due to its tendency to cause complications in immunocompromised patients and its ubiquitous presence in the hospital setting. With the unforgiving emergence of multidrug-resistant strains, it is critical that alternative strategies to control or prevent septic infections in burn patients be developed in parallel with novel antimicrobial agents. In this study, we observed that administration of l-Arg significantly reduced bacterial spread and sepsis in burned mice infected with P. aeruginosa. Given the safety of l-Arg in high doses and its potential wound-healing benefits, this conditionally essential amino acid may represent a useful tool to modulate bacterial behavior in vivo and prevent sepsis in burn patients.

2015 Nelson's Pediatric Antimicrobial Therapy

2015 ◽  
Keyword(s):  
Health Care ◽  
Infectious Diseases ◽  
Health Care Providers ◽  
Antimicrobial Therapy ◽  
Antimicrobial Agents ◽  
Complete Information ◽  
Care Providers ◽  
Dosing Regimens

New! This bestselling and widely used resource on pediatric antimicrobial therapy provides instant access to reliable, up-to-the-minute recommendations for treatment of all infectious diseases in children. For each disease, the authors provide a commentary to help health care providers select the best of all antimicrobial choices. Drug descriptions cover all antimicrobial agents available today, and include complete information about dosing regimens. In response to growing concerns about overuse of antibiotics, the book includes guidelines on when not to prescribe antimicrobials. Key 21st edition features! Contents

scholarly journals Genotyping and antimicrobial resistance in Escherichia coli from pig carcasses

2017 ◽  
Vol 37 (11) ◽  
pp. 1253-1260 ◽  
Author(s):  
Caroline Pissetti ◽  
Gabriela Orosco Werlang ◽  
Jalusa Deon Kich ◽  
Marisa Cardoso
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Commensal Bacteria ◽  
Pfge Analysis ◽  
Gene Detection ◽  
E Coli ◽  
Antimicrobial Resistance Profile ◽  
Resistant Strains ◽  
Pig Carcasses

ABSTRACT: The increasing antimicrobial resistance observed worldwide in bacteria isolated from human and animals is a matter of extreme concern and has led to the monitoring of antimicrobial resistance in pathogenic and commensal bacteria. The aim of this study was to evaluate the antimicrobial resistance profile of Escherichia coli isolated from pig carcasses and to assess the occurrence of relevant resistance genes. A total of 319 E. coli isolates were tested for antimicrobial susceptibility against different antimicrobial agents. Moreover, the presence of extended-spectrum β-lactamase (ESBL) and inducible ampC-β-lactamase producers was investigated. Eighteen multi-resistant strains were chosen for resistance gene detection and PFGE characterization. The study showed that resistance to antimicrobials is widespread in E. coli isolated from pig carcasses, since 86.2% of the strains were resistant to at least one antimicrobial and 71.5% displayed multi-resistance profiles. No ampC-producing isolates were detected and only one ESBL-producing E. coli was identified. Genes strA (n=15), floR (n=14), aac(3)IVa (n=13), tetB (n=13), sul2 (n=12), tetA (n=11), aph(3)Ia (n=8) and sul3 (n=5) were detected by PCR. PFGE analysis of these multi-resistant E. coli strains showed less than 80% similarity among them. We conclude that antimicrobial multi-resistant E. coli strains are common on pig carcasses and present highly diverse genotypes and resistance phenotypes and genotypes.

scholarly journals Comparative In Vitro Activities of AC98-6446, a Novel Semisynthetic Glycopeptide Derivative of the Natural Product Mannopeptimycin α, and Other Antimicrobial Agents against Gram-Positive Clinical Isolates

2004 ◽  
Vol 48 (3) ◽  
pp. 739-746 ◽  
Author(s):  
Peter J. Petersen ◽  
T. Z. Wang ◽  
Russell G. Dushin ◽  
Patricia A. Bradford
Keyword(s):  
Natural Product ◽  
Bactericidal Activity ◽  
Antimicrobial Agents ◽  
Marked Decrease ◽  
Gram Positive ◽  
Novel Structure ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Further Development

ABSTRACT AC98-6446 is a novel semisynthetic cyclic glycopeptide antibiotic related to the natural product mannopeptimycin α (AC98-1). In the present study the activity of AC98-6446 was evaluated against a variety of recent clinical gram-positive pathogens including multiply resistant strains. AC98-6446 demonstrated similar potent activities against methicillin-susceptible and methicillin-resistant staphylococci and glycopeptide-intermediate staphylococcal isolates (MICs at which 90% of isolates are inhibited [MIC90s], 0.03 to 0.06 μg/ml). AC98-6446 also demonstrated good activities against both vancomycin-resistant and -susceptible strains of enterococci (MIC90s, 0.12 and 0.25 μg/ml, respectively) as well as against streptococcal strains (MIC90s, ≤ 0.008 to 0.03 μg/ml). AC98-6446 demonstrated bactericidal activity in terms of the reduction in the viable counts (>3 log10 CFU/ml) of staphylococcal and streptococcal isolates and a marked decrease in the viable counts of most enterococcal strains (from 0.2 to 2.5 log10 CFU/ml). Unlike vancomycin, which demonstrates time-dependent killing, AC98-6446 demonstrated concentration-dependent killing. The potent activity, novel structure, and bactericidal activity demonstrated by AC98-6446 make it an attractive candidate for further development.

scholarly journals Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity

2021 ◽  
Vol 17 (3) ◽  
pp. e1009324
Author(s):  
Lucas dos Santos Dias ◽  
Hannah E. Dobson ◽  
Brock Kingstad Bakke ◽  
Gregory C. Kujoth ◽  
Junfeng Huang ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Influenza A ◽  
Fungal Pathogens ◽  
Animal Studies ◽  
Structural Basis ◽  
Viral Immunity ◽  
Mucosal Vaccination ◽  
Clinical Observations ◽  
Protective Antibodies ◽  
Anti Fungal

The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge.

scholarly journals Light and Phages on Tackle of Infectious Diseases

2021 ◽  
Author(s):  
Felipe de Paula Nogueira Cruz ◽  
Andréa Cristina Bogas ◽  
Cristina Paiva de Sousa
Keyword(s):  
Infectious Diseases ◽  
Antimicrobial Agents ◽  
Microbial Inactivation ◽  
Resistant Bacteria ◽  
Bacteriophage Therapy ◽  
Drug Resistant Bacteria ◽  
Evolutionary Trajectories ◽  
Efficient Alternative ◽  
Emergence Of Resistance ◽  
Inducing Resistance

There has been an important increase in the emergence of resistance in microbial population worldwide. This trajectory needs, necessarily new approaches to treat infectious diseases. The ability to detect and prevent the evolutionary trajectories of microbial resistance would be of value. Photodynamic inactivation (PDI) represents an efficient alternative treatment for diseases caused by viruses, which can cause infections well documented in various mammals. PDI can kill cells after exposure with the appropriate photosensitizer (PS), light of adequate wavelength combined with the presence of oxygen, without inducing resistance. Cytotoxic reactive species formed interaction with vital biomolecules leading to irreversible microbial inactivation. Bacteriophages can act on delivering antimicrobial agents into bacteria, which consist in a likely instrument for the treatment of infectious diseases. Non-enveloped bacteriophages are more difficult to tolerate photoinactivation than enveloped phages, which makes them an important model tool to evaluate the efficiency of PDI therapy against viruses that cause diseases in humans. Combination of photosensitizers and bacteriophage therapy can be employed to eradicate biofilms, contributing to control of infections also caused by drug-resistant bacteria.

scholarly journals The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Arturo Casadevall ◽  
Liise-anne Pirofski ◽  
Michael J. Joyner
Keyword(s):  
Infectious Diseases ◽  
Antimicrobial Agents ◽  
Severe Disease ◽  
Antibody Therapy ◽  
Course Of Disease ◽  
Medical Practitioners ◽  
History Of ◽  
Serum Therapy ◽  
Effective Lessons ◽  
Further Development

ABSTRACT Antibody therapies such as convalescent plasma and monoclonal antibodies have emerged as major potential therapeutics for coronavirus disease 2019 (COVID-19). Immunoglobulins differ from conventional antimicrobial agents in that they mediate direct and indirect antimicrobial effects that work in concert with other components of the immune system. The field of infectious diseases pioneered antibody therapies in the first half of the 20th century but largely abandoned them with the arrival of conventional antimicrobial therapy. Consequently, much of the knowledge gained from the historical development and use of immunoglobulins such as serum and convalescent antibody therapies was forgotten; principles and practice governing their use were not taught to new generations of medical practitioners, and further development of this modality stalled. This became apparent during the COVID-19 pandemic in the spring of 2020 when convalescent plasma was initially deployed as salvage therapy in patients with severe disease. In retrospect, this was a stage of disease when it was less likely to be effective. Lessons of the past tell us that antibody therapy is most likely to be effective when used early in respiratory diseases. This article puts forth three principles of antibody therapy, namely, specificity, temporal, and quantitative principles, connoting that antibody efficacy requires the administration of specific antibody, given early in course of disease in sufficient amount. These principles are traced to the history of serum therapy for infectious diseases. The application of the specificity, temporal, and quantitative principles to COVID-19 is discussed in the context of current use of antibody therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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