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  1. Article ; Online: Evaluation of fecal occult blood testing for rapid diagnosis of invasive diarrhea in young children.

    Kwasi, David A / Adewole, Pelumi D / Akinlabi, Olabisi C / Ekpo, Stella E / Okeke, Iruka N

    PLOS global public health

    2023  Volume 3, Issue 7, Page(s) e0001629

    Abstract: Antimicrobials are only indicated in acute childhood diarrhea if it is invasive or persistent. Rapid screening for invasive diarrhea can therefore inform treatment decisions but pathogen identification by culture is slow, expensive and cumbersome. This ... ...

    Abstract Antimicrobials are only indicated in acute childhood diarrhea if it is invasive or persistent. Rapid screening for invasive diarrhea can therefore inform treatment decisions but pathogen identification by culture is slow, expensive and cumbersome. This study aimed to assess the diagnostic utility of stool microscopy and immunochromatographic fecal occult blood test (FOBT) kits for identifying invasive or potentially invasive diarrhea in Ibadan, Nigeria. Fecal specimens from 46 children under 5 years old with diarrhea, collected as part of ongoing case-control studies, were subjected to stool microscopy for erythrocytes and leucocytes, and FOBT using the innovator's product and four locally procurable generic immunochromatographic kits, each according to manufacturers' instructions. Stool specimens were cultured for enteric bacterial pathogens using standard procedures. Presumptive pathogen isolates were identified biochemically and by PCR, and then confirmed by whole genome sequencing. Shigella, enteroinvasive Escherichia coli and Yersinia, pathogens that invariably cause invasive diarrhea, were detected in five of 46 specimens. Occult blood detection by microscopy was 55.6% sensitive and 78.4% specific, while the innovator's FOBT product was respectively 62.5% and 81.6% sensitive and specific compared to strict invasive pathogen recovery. Microscopy and FOBT testing were less sensitive in identifying specimens that contained pathogens that do not always elicit invasive diarrhea. Generic FOBT tests compared well with the innovator's product. Microscopy and FOBT testing have some value for delineating likely invasive diarrheas. They could inform treatment and serve as early warning indicators for dysentery outbreaks in resource limited settings. Inexpensive, generic FOBT kits that are locally procurable in Nigeria performed as well as the innovator's product.
    Language English
    Publishing date 2023-07-20
    Publishing country United States
    Document type Journal Article
    ISSN 2767-3375
    ISSN (online) 2767-3375
    DOI 10.1371/journal.pgph.0001629
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Antibiofilm agents with therapeutic potential against enteroaggregative Escherichia coli.

    Kwasi, David A / Babalola, Chinedum P / Olubiyi, Olujide O / Hoffmann, Jennifer / Uzochukwu, Ikemefuna C / Okeke, Iruka N

    PLoS neglected tropical diseases

    2022  Volume 16, Issue 10, Page(s) e0010809

    Abstract: Background: Enteroaggregative Escherichia coli (EAEC) is a predominant but neglected enteric pathogen implicated in infantile diarrhoea and nutrient malabsorption. There are no non-antibiotic approaches to dealing with persistent infection by these ... ...

    Abstract Background: Enteroaggregative Escherichia coli (EAEC) is a predominant but neglected enteric pathogen implicated in infantile diarrhoea and nutrient malabsorption. There are no non-antibiotic approaches to dealing with persistent infection by these exceptional colonizers, which form copious biofilms. We screened the Medicines for Malaria Venture Pathogen Box for chemical entities that inhibit EAEC biofilm formation.
    Methodology: We used EAEC strains, 042 and MND005E in a medium-throughput crystal violet-based antibiofilm screen. Hits were confirmed in concentration-dependence, growth kinetic and time course assays and activity spectra were determined against a panel of 25 other EAEC strains. Antibiofilm activity against isogenic EAEC mutants, molecular docking simulations and comparative genomic analysis were used to identify the mechanism of action of one hit.
    Principal findings: In all, five compounds (1.25%) reproducibly inhibited biofilm accumulation by at least one strain by 30-85% while inhibiting growth by under 10%. Hits exhibited potent antibiofilm activity at concentrations at least 10-fold lower than those reported for nitazoxanide, the only known EAEC biofilm inhibitor. Reflective of known EAEC heterogeneity, only one hit was active against both screen isolates, but three hits showed broad antibiofilm activity against a larger panel of strains. Mechanism of action studies point to the EAEC anti-aggregation protein (Aap), dispersin, as the target of compound MMV687800.
    Conclusions: This study identified five compounds, not previously described as anti-adhesins or Gram-negative antibacterials, with significant EAEC antibiofilm activity. Molecule, MMV687800 targets the EAEC Aap. In vitro small-molecule inhibition of EAEC colonization opens a way to new therapeutic approaches against EAEC infection.
    MeSH term(s) Humans ; Escherichia coli/genetics ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Gentian Violet ; Molecular Docking Simulation ; Escherichia coli Infections/drug therapy ; Biofilms ; Complement Inactivating Agents ; Diarrhea
    Chemical Substances Escherichia coli Proteins ; Gentian Violet (J4Z741D6O5) ; Complement Inactivating Agents
    Language English
    Publishing date 2022-10-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0010809
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Quinoline Antimalarials Increase the Antibacterial Activity of Ampicillin.

    Olateju, Olajumoke A / Babalola, Chinedum P / Olubiyi, Olujide O / Kotila, Olayinka A / Kwasi, David A / Oaikhena, Anderson O / Okeke, Iruka N

    Frontiers in microbiology

    2021  Volume 12, Page(s) 556550

    Abstract: Bacterial and malaria co-infections are common in malaria endemic countries and thus necessitate co-administration of antibiotics and antimalarials. There have long been anecdotal clinical reports of interactions between penicillins and antimalarial ... ...

    Abstract Bacterial and malaria co-infections are common in malaria endemic countries and thus necessitate co-administration of antibiotics and antimalarials. There have long been anecdotal clinical reports of interactions between penicillins and antimalarial agents, but the nature and mechanisms of these interactions remain to be investigated. In this study, we employed antimicrobial interaction testing methods to study the effect of two antimalarials on the antibacterial activity of ampicillin
    Language English
    Publishing date 2021-06-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.556550
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Significant Pharmacokinetic Interactions Between Quinine and Ampicillin-Cloxacillin Combination.

    Falade, Olubunmi B / Falusi, Adeyinka G / Olaniyi, Ajibola A / Ezeasor, Chizoba / Kwasi, David A / Babalola, Chinedum P

    Drugs in R&D

    2016  Volume 16, Issue 2, Page(s) 193–203

    Abstract: Introduction: The co-existence of malaria with bacterial infections is common in the tropics, hence the concurrent use of antimalarials and antibiotics.: Objective: This study aimed to investigate the effect on pharmacokinetics and antimicrobial ... ...

    Abstract Introduction: The co-existence of malaria with bacterial infections is common in the tropics, hence the concurrent use of antimalarials and antibiotics.
    Objective: This study aimed to investigate the effect on pharmacokinetics and antimicrobial activity of co-administration of quinine and combined ampicillin-cloxacillin.
    Methods: In total, 14 healthy adults received single oral doses of ampicillin-cloxacillin combination alone and with quinine in a randomized crossover manner. Urine samples collected at predetermined intervals over 48 h were analysed. The effect of quinine on minimum inhibitory concentrations (MICs) of ampicillin and cloxacillin were determined against Staphylococcus aureus by agar diffusion, agar dilution, and broth dilution.
    Results: Quinine significantly reduced the rate and extent of excretion of ampicillin and cloxacillin (p < 0.0002). The total amounts of ampicillin and cloxacillin excreted unchanged (Du(∞)) alone were 217.10 ± 53.82 and 199.0 ± 64.29 mg versus 126.40 ± 50.63 and 135.20 ± 52.24 mg, respectively, with quinine. Respective maximum excretion rates (dDu/dt max) for ampicillin and cloxacillin were 43.55 ± 19.41 and 77.64 ± 29.65 mg/h alone versus 18.01 ± 8.52 and 53.16 ± 20.72 mg/h with quinine. This indicates a significant reduction in Du(∞)and dDu/dt max by 41.78 and 58.65 % for ampicillin and 32.06 and 31.53 % for cloxacillin. Conversely, the disposition of quinine was unaffected by ampicillin-cloxacillin (p > 0.1). The MIC of antibiotics alone versus with quinine, respectively, were 0.11 ± 0.04 and 0.78 ± 0.1 µg/ml for ampicillin, and 0.18 ± 0.1 and 0.92 ± 0.4 µg/ml for cloxacillin, with a five- to sevenfold increase (p > 0.01); indicating a decrease in antimicrobial activity by quinine.
    Conclusions: Quinine therefore, reduced the bioavailability and the antimicrobial activity of ampicillin-cloxacillin upon co-administration, which may have therapeutic implications. Caution is required with the co-administration of these medicines.
    MeSH term(s) Adolescent ; Adult ; Ampicillin/analysis ; Ampicillin/pharmacokinetics ; Ampicillin/urine ; Anti-Bacterial Agents/analysis ; Anti-Bacterial Agents/pharmacokinetics ; Anti-Bacterial Agents/urine ; Antimalarials/analysis ; Antimalarials/pharmacokinetics ; Antimalarials/urine ; Biological Availability ; Chromatography, High Pressure Liquid ; Cloxacillin/analysis ; Cloxacillin/pharmacology ; Cloxacillin/urine ; Cross-Over Studies ; Drug Therapy, Combination ; Female ; Humans ; Male ; Nigeria ; Quinine/analysis ; Quinine/pharmacokinetics ; Quinine/urine ; Staphylococcus aureus/drug effects ; Young Adult
    Chemical Substances Anti-Bacterial Agents ; Antimalarials ; Ampicillin (7C782967RD) ; Quinine (A7V27PHC7A) ; Cloxacillin (O6X5QGC2VB)
    Language English
    Publishing date 2016-06
    Publishing country New Zealand
    Document type Comparative Study ; Journal Article ; Randomized Controlled Trial
    ZDB-ID 2020476-0
    ISSN 1179-6901 ; 1174-5886
    ISSN (online) 1179-6901
    ISSN 1174-5886
    DOI 10.1007/s40268-016-0128-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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