Antimicrobial susceptibility and minimal inhibitory concentration of bacteria isolated from the eyes of dogs with keratoconjunctivitis sicca

ABSTRACT: The objective of this study was to evaluate the antimicrobial susceptibility profile of bacteria isolated from the eyes of dogs with keratoconjunctivitis sicca (KCS). We evaluated 65 dogs diagnosed with KCS and 30 healthy dogs (Control Group). Conjunctival swab samples were collected after KCS was diagnosed. Microbiological examinations were performed, including aerobic culture, antimicrobial susceptibility testing and minimum inhibitory concentration (MIC) determination for chloramphenicol, tobramycin, ofloxacin and moxifloxacin. MICs of the fifteen most resistant strains of Staphylococcus pseudintermedius (Staphylococcus intermedius Group, SIG) and the fifteen most resistant strains of gram-negative bacteria were determined. By percentage, the microorganisms exhibited the highest susceptibility to polymyxin B, tobramycin and chloramphenicol and the lowest to tetracycline. Three multi-drug-resistant strains of SIG were detected: one displayed isolated susceptibility to cefazolin, another to vancomycin, and another to polymyxin B and amikacin. The species of bacteria isolated from the eyes of dogs with KCS presented variable susceptibility to the antibiotics tested. We found evidence of the emergence of quinolone-resistant strains of SIG and further evidence of increased ocular prevalence. These findings reinforce the need to identify the bacteria involved and their antimicrobial susceptibility profile, as secondary infections can serve as exacerbating and perpetuating factors in KCS.

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Use of the NP-40 Detergent-Mediated Assay in Discovery of Inhibitors of β-Hematin Crystallization

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00121-11 ◽

2011 ◽

Vol 55 (7) ◽

pp. 3363-3369 ◽

Cited By ~ 66

Author(s):

Rebecca D. Sandlin ◽

Melissa D. Carter ◽

Patricia J. Lee ◽

Jennifer M. Auschwitz ◽

Susan E. Leed ◽

...

Keyword(s):

Drug Target ◽

Inhibitory Concentration ◽

Protozoan Parasite ◽

Drug Resistant ◽

Digestive Vacuole ◽

Content Type ◽

Parasite Survival ◽

Resistant Strains ◽

Drug Resistant Strains ◽

Important Drug

ABSTRACTThe protozoan parasite responsible for malaria affects over 500 million people each year. Current antimalarials have experienced decreased efficacy due to the development of drug-resistant strains ofPlasmodiumspp., resulting in a critical need for the discovery of new antimalarials. Hemozoin, a crystalline by-product of heme detoxification that is necessary for parasite survival, serves as an important drug target. The quinoline antimalarials, including amodiaquine and chloroquine, act by inhibiting the formation of hemozoin. The formation of this crystal does not occur spontaneously, and recent evidence suggests crystallization occurs in the presence of neutral lipid particles located in the acidic digestive vacuole of the parasite. To mimic these conditions, the lipophilic detergent NP-40 has previously been shown to successfully mediate the formation of β-hematin, synthetic hemozoin. Here, an NP-40 detergent-based assay was successfully adapted for use as a high-throughput screen to identify inhibitors of β-hematin formation. The resulting assay exhibited a favorableZ′ of 0.82 and maximal drift of less than 4%. The assay was used in a pilot screen of 38,400 diverse compounds at a screening concentration of 19.3 μM, resulting in the identification of 161 previously unreported β-hematin inhibitors. Of these, 48 also exhibited ≥90% inhibition of parasitemia in aPlasmodium falciparumwhole-cell assay at a screening concentration of 23 μM. Eight of these compounds were identified to have nanomolar 50% inhibitory concentration values near that of chloroquine in this assay.

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Semi-Synthesis of Marine-Derived Ilamycin F Derivatives and Their Antitubercular Activities

Frontiers in Chemistry ◽

10.3389/fchem.2021.774555 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jun Li ◽

Zhiyong Liu ◽

Mingye Hong ◽

Changli Sun ◽

Tianyu Zhang ◽

...

Keyword(s):

Prevention And Control ◽

Inhibitory Concentration ◽

Drug Resistant ◽

Structure Activity ◽

The World ◽

Resistant Strains ◽

New Challenges ◽

Low Cytotoxicity ◽

Drug Resistant Strains ◽

And Control

Tuberculosis (TB) is still a global disease threatening people’s lives. With the emergence of multi-drug-resistant Mycobacterium tuberculosis the prevention and control of tuberculosis faces new challenges, and the burden of tuberculosis treatment is increasing among the world. Ilamycins are novel cyclopeptides with potent anti-TB activities, which have a unique target protein against M. tuberculosis and drug-resistant strains. Herein, ilamycin F, a major secondary metabolite isolated from the marine-derived mutant strain Streptomyces atratus SCSIO ZH16 ΔilaR, is used as a scaffold to semi-synthesize eighteen new ilamycin derivatives (ilamycin NJL1–NJL18, 1–18). Our study reveals that four of ilamycin NJLs (1, 6, 8, and 10) have slightly stronger anti-TB activities against Mtb H37Rv (minimum inhibitory concentration, 1.6–1.7 μM) compared with that of ilamycin F on day 14th, but obviously display more potent activities than ilamycin F on day 3rd, indicating anti-TB activities of these derivatives with fast-onset effect. In addition, cytotoxic assays show most ilamycin NJLs with low cytotoxicity except ilamycin NJL1 (1). These findings will promote the further exploration of structure-activity relationships for ilamycins and the development of anti-TB drugs.

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Novel isoniazid derivative as promising antituberculosis agent

Future Microbiology ◽

10.2217/fmb-2019-0085 ◽

2020 ◽

Vol 15 (10) ◽

pp. 869-879

Author(s):

Galyna P Volynets ◽

Michail A Tukalo ◽

Volodymyr G Bdzhola ◽

Nataliia M Derkach ◽

Mykola I Gumeniuk ◽

...

Keyword(s):

Resistant Strain ◽

Inhibitory Concentration ◽

Binding Assay ◽

Isonicotinic Acid ◽

Drug Resistant ◽

Major Focus ◽

Unbound Fraction ◽

Protein Binding Assay ◽

Resistant Strains ◽

Drug Resistant Strains

Background: A major focus of tuberculosis drug discovery is aimed at the development of novel antibiotics with activity against drug-resistant strains of Mycobacterium tuberculosis. Results: We have synthesized ten isoniazid derivatives and investigated for antibacterial activity toward M. tuberculosis H37Rv and isoniazid-resistant strain SRI 1369. It was revealed that only one compound, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide (1), is active toward isoniazid-resistant strain with minimum inhibitory concentration value of 0.14 μM. This compound is not cytotoxic toward human liver cells (HepG2; IC50 >100 μM), demonstrates good permeability in Caco-2 cells. Accordingly to the results of plasma protein binding assay, unbound fraction of compound 1, which potentially exhibits pharmacologic effects, is 57.9%. Conclusion: Therefore, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide is a promising compound for further preclinical studies.

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Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens

Scientific Reports ◽

10.1038/s41598-019-50027-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Stéphane L. Benoit ◽

Alan A. Schmalstig ◽

John Glushka ◽

Susan E. Maier ◽

Arthur S. Edison ◽

...

Keyword(s):

Oral Delivery ◽

Galleria Mellonella ◽

Multidrug Resistant ◽

Enteric Pathogens ◽

Control Group ◽

Drug Resistant ◽

Novel Approach ◽

Resistant Strains ◽

Pathogen Colonization ◽

Drug Resistant Strains

Abstract The nickel (Ni)-specific chelator dimethylglyoxime (DMG) has been used for many years to detect, quantitate or decrease Ni levels in various environments. Addition of DMG at millimolar levels has a bacteriostatic effect on some enteric pathogens, including multidrug resistant (MDR) strains of Salmonella Typhimurium and Klebsiella pneumoniae. DMG inhibited activity of two Ni-containing enzymes, Salmonella hydrogenase and Klebsiella urease. Oral delivery of nontoxic levels of DMG to mice previously inoculated with S. Typhimurium led to a 50% survival rate, while 100% of infected mice in the no-DMG control group succumbed to salmonellosis. Pathogen colonization numbers from livers and spleens of mice were 10- fold reduced by DMG treatment of the Salmonella-infected mice. Using Nuclear Magnetic Resonance, we were able to detect DMG in the livers of DMG-(orally) treated mice. Inoculation of Galleria mellonella (wax moth) larvae with DMG prior to injection of either MDR K. pneumoniae or MDR S. Typhimurium led to 40% and 60% survival, respectively, compared to 100% mortality of larvae infected with either pathogen, but without prior DMG administration. Our results suggest that DMG-mediated Ni-chelation could provide a novel approach to combat enteric pathogens, including recalcitrant multi-drug resistant strains.

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Antimicrobial Activity of Extracts of Two Native Fruits of Chile: Arrayan (Luma apiculata) and Peumo (Cryptocarya alba)

Antibiotics ◽

10.3390/antibiotics9080444 ◽

2020 ◽

Vol 9 (8) ◽

pp. 444

Author(s):

Jitka Viktorová ◽

Rohitesh Kumar ◽

Kateřina Řehořová ◽

Lan Hoang ◽

Tomas Ruml ◽

...

Keyword(s):

Mass Spectrometry ◽

Inhibitory Concentration ◽

Dependent Manner ◽

Drug Resistant ◽

Planktonic Cells ◽

Fruit Extract ◽

Concentration Dependent Manner ◽

Autoinducer 2 ◽

Resistant Strains ◽

Drug Resistant Strains

Arrayan and peumo fruits are commonly used in the traditional medicine of Chile. In this study, the concentration of the extracts halving the bacterial viability and biofilms formation and disruption of the drug-sensitive and drug-resistant strains of Staphylococcus aureus and Pseudomonas aeruginosa was determined. The chemical composition of extracts was analyzed by high-resolution liquid chromatography coupled with mass spectrometry (U-HPLC/MS). The arrayan extract (Inhibitory concentration IC50 0.35 ± 0.01 mg/mL) was more effective than peumo extract (IC50 0.53 ± 0.02 mg/mL) in the inhibition of S. aureus planktonic cells. Similarly, the arrayan extract was more effective in inhibiting the adhesion (S. aureus IC50 0.23 ± 0.02 mg/mL, P. aeruginosa IC50 0.29 ± 0.02 mg/mL) than peumo extracts (S. aureus IC50 0.47 ± 0.03 mg/mL, P. aeruginosa IC50 0.35 ± 0.01 mg/mL). Both extracts inhibited quorum sensing in a concentration-dependent manner, and the most significant was the autoinducer-2 type communication inhibition by arrayan extract. Both extracts also disrupted preformed biofilm of P. aeruginosa (arrayan IC50 0.56 ± 0.04 mg/mL, peumo IC50 0.59 ± 0.04 mg/mL). However, neither arrayan nor peumo extracts disrupted S. aureus mature biofilm. U-HPLC/MS showed that both fruit extracts mainly possessed quercetin compounds; the peumo fruit extract also contained phenolic acids and phenylpropanoids. Our results suggested that both extracts could be used as natural antimicrobials for some skin and nosocomial infections.

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Activities of tubercular inflammation (on the morphological data) with different duration in the patients with drug-resistant pulmonary tuberculosis

Journal of New Medical Technologies eJournal ◽

10.12737/18556 ◽

2016 ◽

Vol 10 (1) ◽

pp. 0-0

Author(s):

Елипашев ◽

A. Elipashev ◽

Никольский ◽

V. Nikolskiy ◽

Шпрыков ◽

...

Keyword(s):

Drug Resistance ◽

High Sensitivity ◽

Morphological Data ◽

Control Group ◽

Drug Resistant ◽

Specific Therapy ◽

Resistant Tuberculosis ◽

Number Of Patients ◽

Resistant Strains ◽

Drug Resistant Strains

The purpose of this research was to determine the dependence of the tubercular inflammation activity of varying duration of the disease and drug resistance. Morphological activity of inflammation in 161 patients with drug-resistant and 149 patients with retaining its high sensitivity was studied. Morphological assessment of the activity of specific changes in tuberculosis was carried out according to the B.M. Ariel classification (1998). It was revealed at morphologic study of resection material that the greatest activity of specific inflammation and its prevalence outside the main lesion was in the group of patients limited with drug resistance tuberculosis. It was noted the prevalence of IV-V degree of morphological activity of tubercular process in the study group by 3 times over the control group with disease duration of more than 1 year. Predominance of widespread active specific changes (IV degree) was determined in 2 times for the first educed patients of basic group with drug-resistant above a control group. This is due to increasing the number of patients with cavernous and fibro-cavernous tuberculosis.Thus, it is necessary to operate patients with drug-resistant tuberculosis as soon as possi-ble after adequate specific therapy and the presence of the signs of stabilization process, because as the full stabilization of tuberculosis process did not achieve according to the morphological study of surgical specimens in the preoperative period. Further specific therapy becomes futile due to the rise of drug resistance, the emer-gence of new drug-resistant strains of Mycobacterium tuberculosis.

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Synergistic Antimycobacterial Actions ofKnowltonia vesicatoria(L.f) Sims

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/808979 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Antoinette Labuschagné ◽

Ahmed A. Hussein ◽

Benjamín Rodríguez ◽

Namrita Lall

Keyword(s):

South African ◽

Inhibitory Concentration ◽

Ethanol Extract ◽

Antimycobacterial Activity ◽

First Report ◽

Pelargonium Sidoides ◽

Resistant Strains ◽

African Plants ◽

Drug Resistant Strains ◽

Euclea Natalensis

Euclea natalensisA.DC.,Knowltonia vesicatoria(L.f) Sims, andPelargonium sidoidesDC. are South African plants traditionally used to treat tuberculosis. Extracts from these plants were used in combination with isoniazid (INH) to investigate the possibility of synergy with respect to antimycobacterial activity. The ethanol extract ofK. vesicatoriawas subjected to fractionation to identify the active compounds. The activity of theKnowltoniaextract remained superior to the fractions with a minimum inhibitory concentration (MIC) of 625.0 μg/mL againstMycobacterium smegmatisand an MIC of 50.00 μg/mL againstM. tuberculosis. TheK. vesicatoriaextract was tested against two different drug-resistant strains ofM. tuberculosis, which resulted in an MIC of 50.00 μg/mL on both strains. The combination ofK. vesicatoriawith INH exhibited the best synergistic antimycobacterial activity with a fractional inhibitory concentration index of 0.25 (a combined concentration of 6.28 μg/mL). A fifty percent inhibitory concentration of this combination against U937 cells was 121.0 μg/mL. Two compounds, stigmasta-5,23-dien-3-ol (1) and 5-(hydroxymethyl)furan-2(5H)-one (2), were isolated fromK. vesicatoriaas the first report of isolation for both compounds from this plant and the first report of antimycobacterial activity. Compound (1) was active against drug-sensitiveM. tuberculosiswith an MIC of 50.00 μg/mL.

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A Novel Innate Immune-Enhancement Strategy Combined with IVIG Rescues Mice from FatalStaphylococcus aureusSepticemia

International Journal of Microbiology ◽

10.1155/2011/725483 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Gowrisankar Rajam ◽

Gabrielle M. Hammons ◽

George M. Carlone ◽

Jacquelyn S. Sampson ◽

Edwin W. Ades

Keyword(s):

Immune Therapy ◽

Innate Immune ◽

Control Group ◽

Amino Acid Peptide ◽

Resistant Strains ◽

Immune Enhancement ◽

Opsonophagocytic Killing ◽

Drug Resistant Strains

Staphylococcus aureus(SA) is a major community-acquired pathogen. The emergence of drug-resistant strains like, methicillin-resistant SA (MRSA), poses stiff challenges to therapeutic intervention. Passive immune-therapy with specific antibodies is being actively examined to treat fulminant infections with limited success. In this study, we demonstrate that P4, a 28-amino acid peptide, derived from pneumococcal surface adhesin A along with pathogen-specific antibody (IVIG; P4 therapy) is successful in enhancing the opsonophagocytic killing (OPK) ofS. aureus in vitro. We questioned if it is possible to expand P4 therapy to treat staphylococcal infectionsin vivo. P4 therapy in combination with IVIG rescued 7/10 morbidly illS. aureus-infected mice while only 2/10 survived in the control group.

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Successful Treatment of Postneurosurgical Ventriculitis Caused by Extensively Drug-resistant Acinetobacter baumannii in a Child: Case Report

Jundishapur Journal of Microbiology ◽

10.5812/jjm.118114 ◽

2022 ◽

Vol 14 (2) ◽

Author(s):

Rui Yang ◽

Fang Li ◽

Wei Wei Mao ◽

Xin Wei ◽

Xinzhu Liu ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Intraventricular Hemorrhage ◽

Therapeutic Option ◽

Polymyxin B ◽

External Ventricular Drainage ◽

Drug Resistant ◽

Ventricular Drainage ◽

Extensively Drug Resistant ◽

Resistant Strains ◽

Drug Resistant Strains

Introduction: The incidence of postneurosurgical Acinetobacter baumannii ventriculitis/meningitis, primarily due to drug-resistant strains, has increased considerably in recent years. However, limited therapeutic options are available because most antibiotics poorly penetrate the blood-brain barrier, especially in pediatric patients. Case Presentation: A five-year-old boy developed ventriculitis due to extensively drug-resistant A. baumannii (XDRAB) after bilateral frontal external ventricular drainage for spontaneous intraventricular hemorrhage. The boy was safely and successfully treated with intraventricular (IVT)/intrathecal (ITH) polymyxin B together with intravenous tigecycline plus cefoperazone/sulbactam. Conclusions: In the present case, postneurosurgical XDRAB ventriculitis was closely associated with intraventricular hemorrhage and the placement of external ventricular drainage. IVT/ITH polymyxin B combined with intravenous tigecycline and cefoperazone sulbactam could be a therapeutic option against XDRAB ventriculitis in children.

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Omadacycline Potentiates Clarithromycin Activity Against Mycobacterium abscessus

Frontiers in Pharmacology ◽

10.3389/fphar.2021.790767 ◽

2021 ◽

Vol 12 ◽

Author(s):

Bui Thi Bich Hanh ◽

Nguyen Thanh Quang ◽

Yujin Park ◽

Bo Eun Heo ◽

Seunghyeon Jeon ◽

...

Keyword(s):

Concentration Index ◽

Inhibitory Concentration ◽

Mycobacterium Abscessus ◽

Respiratory Pathogen ◽

Drug Resistant ◽

Zebrafish Model ◽

Resistant Strains ◽

Drug Resistant Strains ◽

Positive Effect

Mycobacterium abscessus is a difficult respiratory pathogen to treat, when compared to other nontuberculus mycobacteria (NTM), due to its drug resistance. In this study, we aimed to find a new clarithromycin partner that potentiated strong, positive, synergy against M. abscessus among current anti-M. abscessus drugs, including omadacycline, amikacin, rifabutin, bedaquiline, and cefoxitine. First, we determined the minimum inhibitory concentrations required of all the drugs tested for M. abscessus subsp. abscessus CIP104536T treatment using a resazurin microplate assay. Next, the best synergistic partner for clarithromycin against M. abscessus was determined using an in vitro checkerboard combination assay. Among the drug combinations evaluated, omadacycline showed the best synergistic effect with clarithromycin, with a fractional inhibitory concentration index of 0.4. This positive effect was also observed against M. abscessus clinical isolates and anti-M. abscessus drug resistant strains. Lastly, this combination was further validated using a M. abscessus infected zebrafish model. In this model, the clarithromycin-omadacyline regimen was found to inhibit the dissemination of M. abscessus, and it significantly extended the lifespan of the M. abscessus infected zebrafish. In summation, the synergy between two anti-M. abscessus compounds, clarithromycin and omadacycline, provides an attractive foundation for a new M. abscessus treatment regimen.

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