scholarly journals Imidocarb Dipropionate Clears Persistent Babesia caballi Infection with Elimination of Transmission Potential

2009 ◽  
Vol 53 (10) ◽  
pp. 4327-4332 ◽  
Author(s):  
O. Nicolas Schwint ◽  
Massaro W. Ueti ◽  
Guy H. Palmer ◽  
Lowell S. Kappmeyer ◽  
Melissa T. Hines ◽  
...  

ABSTRACT Antimicrobial treatment of persistent infection to eliminate transmission risk represents a specific challenge requiring compelling evidence of complete pathogen clearance. The limited repertoire of antimicrobial agents targeted at protozoal parasites magnifies this challenge. Using Babesia caballi as both a model and a specific apicomplexan pathogen for which evidence of the elimination of transmission risk is required for international animal movement, we tested whether a high-dose regimen of imidocarb dipropionate cleared infection from persistently infected asymptomatic horses and/or eliminated transmission risk. Clearance with elimination of transmission risk was supported by the following four specific lines of evidence: (i) inability to detect parasites by quantitative PCR and nested PCR amplification, (ii) conversion from seropositive to seronegative status, (iii) inability to transmit infection by direct inoculation of blood into susceptible recipient horses, and (iv) inability to transmit infection by ticks acquisition fed on the treated horses and subsequently transmission fed on susceptible horses. In contrast, untreated horses remained infected and capable of transmitting B. caballi using the same criteria. These findings establish that imidocarb dipropionate treatment clears B. caballi infection with confirmation of lack of transmission risk either by direct blood transfer or a high tick burden. Importantly, the treated horses revert to seronegative status according to the international standard for serologic testing and would be permitted to move between countries where the pathogen is endemic and countries that are free of the pathogen.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Divine Ekwem ◽  
Thomas A. Morrison ◽  
Richard Reeve ◽  
Jessica Enright ◽  
Joram Buza ◽  
...  

AbstractIn Africa, livestock are important to local and national economies, but their productivity is constrained by infectious diseases. Comprehensive information on livestock movements and contacts is required to devise appropriate disease control strategies; yet, understanding contact risk in systems where herds mix extensively, and where different pathogens can be transmitted at different spatial and temporal scales, remains a major challenge. We deployed Global Positioning System collars on cattle in 52 herds in a traditional agropastoral system in western Serengeti, Tanzania, to understand fine-scale movements and between-herd contacts, and to identify locations of greatest interaction between herds. We examined contact across spatiotemporal scales relevant to different disease transmission scenarios. Daily cattle movements increased with herd size and rainfall. Generally, contact between herds was greatest away from households, during periods with low rainfall and in locations close to dipping points. We demonstrate how movements and contacts affect the risk of disease spread. For example, transmission risk is relatively sensitive to the survival time of different pathogens in the environment, and less sensitive to transmission distance, at least over the range of the spatiotemporal definitions of contacts that we explored. We identify times and locations of greatest disease transmission potential and that could be targeted through tailored control strategies.


1994 ◽  
Vol 103 (5_suppl) ◽  
pp. 11-14 ◽  
Author(s):  
Daniel M. Canafax ◽  
G. Scott Giebink

Episodes of acute otitis media frequently occur in childhood and are attended by significant morbidity, such as hearing loss and possible speech delay. Bacteria play an important etiologic role in the pathogenesis of otitis media; therefore, antimicrobial agents are the cornerstone in the treatment of this disease. Many antimicrobial choices are available for treating children with acute otitis media. To choose an antimicrobial for each patient, consideration must be given to the patient's age, history of otitis media episodes, and responses to previously used antimicrobial drugs, and the regional antimicrobial susceptibility of the otitis media pathogens.


PEDIATRICS ◽  
1998 ◽  
Vol 101 (Supplement_1) ◽  
pp. 163-165 ◽  
Author(s):  
Scott F. Dowell ◽  
S. Michael Marcy ◽  
William R. Phillips ◽  
Michael A. Gerber ◽  
Benjamin Schwartz

This article introduces a set of principles to define judicious antimicrobial use for five conditions that account for the majority of outpatient antimicrobial use in the United States. Data from the National Center for Health Statistics indicate that in recent years, approximately three fourths of all outpatient antibiotics have been prescribed for otitis media, sinusitis, bronchitis, pharyngitis, or nonspecific upper respiratory tract infection.1Antimicrobial drug use rates are highest for children1; therefore, the pediatric age group represents the focus for the present guidelines. The evidence-based principles presented here are focused on situations in which antimicrobial therapy could be curtailed without compromising patient care. They are not formulated as comprehensive management strategies. For most upper respiratory infections that require antimicrobial treatment, there are several appropriate oral agents from which to choose. Although the general principles of selecting narrow-spectrum agents with the fewest side effects and lowest cost are important, the principles that follow include few specific antibiotic selection recommendations.


2001 ◽  
Vol 45 (5) ◽  
pp. 1343-1348 ◽  
Author(s):  
Hisakazu Yano ◽  
Akio Kuga ◽  
Ryoichi Okamoto ◽  
Hidero Kitasato ◽  
Toshimitsu Kobayashi ◽  
...  

ABSTRACT In 1996, Serratia marcescens KU3838 was isolated from the urine of a patient with a urinary tract infection at a hospital in northern Japan and was found to contain the plasmid pKU501. Previously, we determined that pKU501 carries bla IMP and the genes for TEM-1-type β-lactamases as well as producing both types of β-lactamases (H. Yano, A. Kuga, K. Irinoda, R. Okamoto, T. Kobayashi, and M. Inoue, J. Antibiot. 52:1135–1139, 1999). pKU502 is a recombinant plasmid that contains a 1.5-kb DNA fragment, including the metallo-β-lactamase gene, and is obtained by PCR amplification of pKU501. The sequence of the metallo-β-lactamase gene in pKU502 was determined and revealed that this metallo-β-lactamase gene differed from the gene encoding IMP-1 by one point mutation, leading to one amino acid substitution: 640-A in the base sequence of the IMP-1 gene was replaced by G, and Ser-196 was replaced by Gly in the mature enzyme. This enzyme was designated IMP-6. The strains that produced IMP-6 were resistant to carbapenems. The MICs of panipenem and especially meropenem were higher than the MIC of imipenem for these strains. The k cat/Km value of IMP-6 was about sevenfold higher against meropenem than against imipenem, although the MIC of meropenem for KU1917, which produced IMP-1, was lower than that of imipenem, and the MIC of panipenem was equal to that of imipenem. These results support the hypothesis that IMP-6 has extended substrate profiles against carbapenems. However, the activity of IMP-6 was very low against penicillin G and piperacillin. These results suggest that IMP-6 acquired high activity against carbapenems, especially meropenem, via the point mutation but in the process lost activity against penicillins. Although IMP-6 has reduced activity against penicillins due to this point mutation, pKU501 confers resistance to a variety of antimicrobial agents because it also produces TEM-1-type enzyme.


1997 ◽  
Vol 41 (11) ◽  
pp. 2389-2393 ◽  
Author(s):  
Y Kashida ◽  
M Kato

Fluoroquinolone antibacterial agents have been reported to induce tendon lesions in juvenile rats. In the present study, we characterized fluoroquinolone-induced Achilles tendon lesions by comparing the effects of 10 fluoroquinolones and examining the potential of one of these antimicrobial agents, pefloxacin, to induce tendon lesions when coadministered with one of nine anti-inflammatory compounds. Among the 10 fluoroquinolones tested, fleroxacin and pefloxacin were the most toxic, inducing lesions at a dose of 100 mg/kg of body weight or more, while lomefloxacin, levofloxacin, and ofloxacin or sparfloxacin and enoxacin induced lesions at 300 mg/kg or more and 900 mg/kg, respectively. In contrast, norfloxacin, ciprofloxacin, and tosufloxacin had no effect even at the high dose of 900 mg/kg. The severity of the Achilles tendon lesions appeared to correlate with the structure of the substituent at the seventh position. Furthermore, pefloxacin-induced tendon lesions were inhibited by coadministration with dexamethasone and N-nitro-L-arginine methyl ester. Phenidone (1-phenyl-3-pyrazolidinone) and 2-(12-hydroxydodeca-5,10-diynyl)3,5,6-trimethyl-1,4-benzoqui none (AA861) also decreased the incidence of tendon lesions. In contrast, catalase, dimethyl sulfoxide, indomethacin, pyrilamine, and cimetidine did not modify these tendon lesions. These results suggest that nitric oxide and 5-lipoxigenase products partly mediate fluoroquinolone-induced tendon lesions.


2019 ◽  
Author(s):  
Emir Hodzic ◽  
Denise M. Imai ◽  
Edlin Escobar

ABSTRACTA basic feature of infection caused byBorrelia burgdorferi, the etiological agent of Lyme borreliosis, is that persistent infection is the rule, not the norm, in its many hosts. The ability to persist and evade host immune clearance poses a challenge to effective antimicrobial treatment. A link between therapy failure and the presence of persister cells has started to emerge. There is growing experimental evidence that viable, but non-cultivable spirochetes persist following treatment with several different antimicrobial agents, then resurge after 12 months. The current study utilized the mouse model to evaluate if persistence and resurgence occur following antimicrobial treatment in a disease-susceptible (C3H/HeN) and disease-resistant (C57BL/6) mouse strain infected withB. burgdorferistrains N40 and B31, to confirm the generality of these phenomena. The status of infection was evaluated at 12 and 18-months after treatment. The results demonstrated that persistent spirochetes remain viable for up to 18 months following treatment, but divide slowly, thereby being tolerant to the effects of antimicrobial agents, as well as being non-cultivable. The phenomenon of persistence and resurgence in disease-susceptible C3H mice is equally evident in disease-resistant B6 mice, and not unique to any particularB. burgdorferistrain. The results also demonstrate that following antimicrobial treatment, both strains ofB. burgdorferi, N40 and B31, lose one or more small plasmids, resulting in attenuation. The biological relevance of attenuatedB. burgdorferispirochetes is probably inconsequential. The study demonstrated that non-cultivable spirochetes can persist in a host following antimicrobial treatment for a long time but did not demonstrate their clinical relevance in a mouse model of chronic infection.


2021 ◽  
Vol 14 (2) ◽  
pp. e239618
Author(s):  
Brian Alexander Hummel ◽  
Julie Blackburn ◽  
Anne Pham-Huy ◽  
Katherine Muir

Cerebral vasculitis is a serious complication of bacterial meningitis that can cause significant morbidity and mortality due to stroke. Currently, there are no treatment guidelines or safety and efficacy studies on the management of cerebral vasculitis in this context. Herein, we report a case of a previously well 11-year-old girl who presented with acute otitis media that progressed to mastoiditis and fulminant meningitis. Group A Streptococcus was found in blood and ear-fluid cultures (lumbar puncture was unsuccessful). Her decreased level of consciousness persisted despite appropriate antimicrobial treatment, and repeat MRI revealed extensive large vessel cerebral vasculitis. Based on expert opinion and a presumed inflammatory mechanism, her cerebral vasculitis was treated with 7 days of pulse intravenous methylprednisolone followed by oral prednisone taper. She was also treated with intravenous heparin. Following these therapies, she improved clinically and radiographically with no adverse events. She continues to undergo rehabilitation with improvement.


Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 969
Author(s):  
Mateusz Cieśluk ◽  
Piotr Deptuła ◽  
Ewelina Piktel ◽  
Krzysztof Fiedoruk ◽  
Łukasz Suprewicz ◽  
...  

Despite the hope that was raised with the implementation of antibiotics to the treatment of infections in medical practice, the initial enthusiasm has substantially faded due to increasing drug resistance in pathogenic microorganisms. Therefore, there is a need for novel analytical and diagnostic methods in order to extend our knowledge regarding the mode of action of the conventional and novel antimicrobial agents from a perspective of single microbial cells as well as their communities growing in infected sites, i.e., biofilms. In recent years, atomic force microscopy (AFM) has been mostly used to study different aspects of the pathophysiology of noninfectious conditions with attempts to characterize morphological and rheological properties of tissues, individual mammalian cells as well as their organelles and extracellular matrix, and cells’ mechanical changes upon exposure to different stimuli. At the same time, an ever-growing number of studies have demonstrated AFM as a valuable approach in studying microorganisms in regard to changes in their morphology and nanomechanical properties, e.g., stiffness in response to antimicrobial treatment or interaction with a substrate as well as the mechanisms behind their virulence. This review summarizes recent developments and the authors’ point of view on AFM-based evaluation of microorganisms’ response to applied antimicrobial treatment within a group of selected bacteria, fungi, and viruses. The AFM potential in development of modern diagnostic and therapeutic methods for combating of infections caused by drug-resistant bacterial strains is also discussed.


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