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Levofloxacin Pharmacokinetics/Pharmacodynamics, Dosing, Susceptibility Breakpoints, and Artificial Intelligence in the Treatment of Multidrug-resistant Tuberculosis

Deshpande, Devyani ; Pasipanodya, Jotam G ; Mpagama, Stellah G ; [et al.]

Oxford University Press (OUP) ; 2018

In: Clinical Infectious Diseases Vol. 67, No. suppl_3 ( 2018-11-28), p. S293-S302

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In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 67, No. suppl_3 ( 2018-11-28), p. S293-S302

Type of Medium: Online Resource

ISSN: 1058-4838 , 1537-6591

URL: Article

DOI: 10.1093/cid/ciy611

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Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2018

detail.hit.zdb_id: 2002229-3

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Pharmacokinetic-Pharmacodynamic Determinants of Clinical Outcomes for Rifampin-Resistant Tuberculosis: A Multisite Prospective Cohort Study

Heysell, Scott K ; Mpagama, Stellah G ; Ogarkov, Oleg B ; [et al.]

Oxford University Press (OUP) ; 2023

In: Clinical Infectious Diseases Vol. 76, No. 3 ( 2023-02-08), p. 497-505

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In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 76, No. 3 ( 2023-02-08), p. 497-505

Abstract: Rifampin-resistant and/or multidrug-resistant tuberculosis (RR/MDR-TB) treatment requires multiple drugs, and outcomes remain suboptimal. Some drugs are associated with improved outcome. It is unknown whether particular pharmacokinetic-pharmacodynamic relationships predict outcome. Methods Adults with pulmonary RR/MDR-TB in Tanzania, Bangladesh, and the Russian Federation receiving local regimens were enrolled from June 2016 to July 2018. Serum was collected after 2, 4, and 8 weeks for each drug’s area under the concentration-time curve over 24 hours (AUC0–24). Quantitative susceptibility of the M. tuberculosis isolate was measured by minimum inhibitory concentrations (MICs). Individual drug AUC0–24/MIC targets were assessed by adjusted odds ratios (ORs) for favorable treatment outcome, and hazard ratios (HRs) for time to sputum culture conversion. K-means clustering algorithm separated the cohort of the most common multidrug regimen into 4 clusters by AUC0–24/MIC exposures. Results Among 290 patients, 62 (21%) experienced treatment failure, including 30 deaths. Moxifloxacin AUC0–24/MIC target of 58 was associated with favorable treatment outcome (OR, 3.75; 95% confidence interval, 1.21–11.56; P = .022); levofloxacin AUC0–24/MIC of 118.3, clofazimine AUC0–24/MIC of 50.5, and pyrazinamide AUC0–24 of 379 mg × h/L were associated with faster culture conversion (HR & gt;1.0, P & lt; .05). Other individual drug exposures were not predictive. Clustering by AUC0–24/MIC revealed that those with the lowest multidrug exposures had the slowest culture conversion. Conclusions Amidst multidrug regimens for RR/MDR-TB, serum pharmacokinetics and M. tuberculosis MICs were variable, yet defined parameters to certain drugs—fluoroquinolones, pyrazinamide, clofazimine—were predictive and should be optimized to improve clinical outcome. Clinical Trials Registration NCT03559582.

Type of Medium: Online Resource

ISSN: 1058-4838 , 1537-6591

URL: Article

DOI: 10.1093/cid/ciac511

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XA 10000

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2023

detail.hit.zdb_id: 2002229-3

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3

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Experiences and perceptions of participants on the pathway towards clinical management of dual tuberculosis and diabetes mellitus in Tanzania

Chamba, Nyasatu G. ; Byashalira, Kenneth C. ; Christensen, Dirk L. ; [et al.]

Informa UK Limited ; 2022

In: Global Health Action Vol. 15, No. 1 ( 2022-12-31)

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In: Global Health Action, Informa UK Limited, Vol. 15, No. 1 ( 2022-12-31)

Type of Medium: Online Resource

ISSN: 1654-9716 , 1654-9880

URL: Article

DOI: 10.1080/16549716.2022.2143044

Language: English

Publisher: Informa UK Limited

Publication Date: 2022

detail.hit.zdb_id: 2540569-X

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Implementing Innovative Approaches to Improve Health Care Delivery Systems for Integrating Communicable and Non-Communicable Diseases Using Tuberculosis and Diabetes as a Model in Tanzania

Mpagama, Stellah G. ; Byashalira, Kenneth C. ; Chamba, Nyasatu G. ; [et al.]

MDPI AG ; 2023

In: International Journal of Environmental Research and Public Health Vol. 20, No. 17 ( 2023-08-29), p. 6670-

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In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 20, No. 17 ( 2023-08-29), p. 6670-

Abstract: Background: Many evidence-based health interventions, particularly in low-income settings, have failed to deliver the expected impact. We designed an Adaptive Diseases Control Expert Programme in Tanzania (ADEPT) to address systemic challenges in health care delivery and examined the feasibility, acceptability and effectiveness of the model using tuberculosis (TB) and diabetes mellitus (DM) as a prototype. Methods: This was an effectiveness-implementation hybrid type-3 design that was implemented in Dar es Salaam, Iringa and Kilimanjaro regions. The strategy included a stepwise training approach with web-based platforms adapting the Gibbs’ reflective cycle. Health facilities with TB services were supplemented with DM diagnostics, including glycated haemoglobin A1c (HbA1c). The clinical audit was deployed as a measure of fidelity. Retrospective and cross-sectional designs were used to assess the fidelity, acceptability and feasibility of the model. Results: From 2019–2021, the clinical audit showed that ADEPT intervention health facilities more often identified median 8 (IQR 6–19) individuals with dual TB and DM, compared with control health facilities, median of 1 (IQR 0–3) (p = 0.02). Likewise, the clinical utility of HbA1c on intervention sites was 63% (IQR:35–75%) in TB/DM individuals compared to none in the control sites at all levels, whereas other components of the standard of clinical management of patients with dual TB and DM did not significantly differ. The health facilities showed no difference in screening for additional comorbidities such as hypertension and malnutrition. The stepwise training enrolled a total of 46 nurse officers and medical doctors/specialists for web-based training and 40 (87%) attended the workshop. Thirty-one (67%), 18 nurse officers and 13 medical doctors/specialists, implemented the second step of training others and yielded a total of 519 additional front-line health care workers trained: 371 nurses and 148 clinicians. Overall, the ADEPT model was scored as feasible by metrics applied to both front-line health care providers and health facilities. Conclusions: It was feasible to use a stepwise training and clinical audit to support the integration of TB and DM management and it was largely acceptable and effective in differing regions within Tanzania. When adapted in the Tanzania health system context, the model will likely improve quality of services.

Type of Medium: Online Resource

ISSN: 1660-4601

URL: Article

DOI: 10.3390/ijerph20176670

Language: English

Publisher: MDPI AG

Publication Date: 2023

detail.hit.zdb_id: 2175195-X

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5

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d -Cycloserine Pharmacokinetics/Pharmacodynamics, Susceptibility, and Dosing Implications in Multidrug-resistant Tuberculosis: A Faustian Deal

Deshpande, Devyani ; Alffenaar, Jan-Willem C ; Köser, Claudio U ; [et al.]

Oxford University Press (OUP) ; 2018

In: Clinical Infectious Diseases Vol. 67, No. suppl_3 ( 2018-11-28), p. S308-S316

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In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 67, No. suppl_3 ( 2018-11-28), p. S308-S316

Type of Medium: Online Resource

ISSN: 1058-4838 , 1537-6591

URL: Article

DOI: 10.1093/cid/ciy624

RVK:

XA 10000

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2018

detail.hit.zdb_id: 2002229-3

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Ethionamide Pharmacokinetics/Pharmacodynamics-derived Dose, the Role of MICs in Clinical Outcome, and the Resistance Arrow of Time in Multidrug-resistant Tuberculosis

Deshpande, Devyani ; Pasipanodya, Jotam G ; Mpagama, Stellah G ; [et al.]

Oxford University Press (OUP) ; 2018

In: Clinical Infectious Diseases Vol. 67, No. suppl_3 ( 2018-11-28), p. S317-S326

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In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 67, No. suppl_3 ( 2018-11-28), p. S317-S326

Type of Medium: Online Resource

ISSN: 1058-4838 , 1537-6591

URL: Article

DOI: 10.1093/cid/ciy609

RVK:

XA 10000

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2018

detail.hit.zdb_id: 2002229-3

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Impact of early diagnosis of impaired glucose regulation in tuberculosis: Comparison of clinical outcomes in people with tuberculosis in Tanzania

Byashalira, Kenneth C. ; Chamba, Nyasatu G. ; Alkabab, Yosra ; [et al.]

Wiley ; 2022

In: Tropical Medicine & International Health Vol. 27, No. 9 ( 2022-09), p. 815-822

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In: Tropical Medicine & International Health, Wiley, Vol. 27, No. 9 ( 2022-09), p. 815-822

Abstract: Diabetes mellitus (DM) has been known to compromise tuberculosis (TB) treatment outcomes. Association data are limited for early hyperglycaemia detection and TB treatment outcomes. Thus, we assessed treatment outcomes including time to sputum conversion and death in TB participants with or without hyperglycaemia. Methods A prospective cohort study recruited TB participants receiving anti‐TB treatment at health facilities in Tanzania between October 2019 and September 2020. Hyperglycaemia was defined as having pre‐existing DM or pre‐treatment random blood glucose of ≥7.8 mmol/L, in combination categorised as impaired glucose regulation (IGR). Those with IGR were further screened for hyperglycaemia severity using glycated haemoglobin. In case of unknown status, participants were tested for HIV. Time to death was determined at 6 months of TB treatment. Results Of 1344 participants, 187 (13.9%) had IGR, of whom 44 (23.5%) were HIV co‐infected. Overall treatment success was 1206 (89.7%), and was similar among participants with or without IGR ( p 〉 0.05). Time to death for participants with and without IGR was 18 versus 28 days ( p = 0.870), respectively. Age ≥ 40 years ( p = 0.038), bacteriological positive ( p = 0.039), HIV ( p = 0.009), or recurrent TB ( p = 0.017) predicted death or treatment success during TB treatment in adjusted multivariable models. Conclusion IGR did not influence clinical outcomes in TB patients with or without IGR in a programme of early IGR diagnosis and integration TB, HIV and DM care. Early detection and co‐management of multi‐morbidities among people diagnosed with TB may reduce likelihood of poor treatment outcomes in a programmatic setting.

Type of Medium: Online Resource

ISSN: 1360-2276 , 1365-3156

URL: Issue

URL: Article

DOI: 10.1111/tmi.v27.9

DOI: 10.1111/tmi.13806

Language: English

Publisher: Wiley

Publication Date: 2022

detail.hit.zdb_id: 2018112-7

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Where can Tanzania health system integrate clinical management of patients with dual tuberculosis and diabetes mellitus? A cross-sectional survey at varying levels of health facilities

Chamba, Nyasatu G. ; Byashalira, Kenneth C. ; Shayo, PendoMartha J. ; [et al.]

Elsevier BV ; 2022

In: Public Health in Practice Vol. 3 ( 2022-06), p. 100242-

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In: Public Health in Practice, Elsevier BV, Vol. 3 ( 2022-06), p. 100242-

Type of Medium: Online Resource

ISSN: 2666-5352

URL: Article

DOI: 10.1016/j.puhip.2022.100242

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 3041067-8

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Gridlock from diagnosis to treatment of multidrug resistant tuberculosis (MDR-TB) in Tanzania: patients’ perspectives from a focus group discussion

Mpagama, Stellah G. ; Ezekiel, Mangi J. ; Mbelele, Peter M. ; [et al.]

Springer Science and Business Media LLC ; 2020

In: BMC Public Health Vol. 20, No. 1 ( 2020-12)

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In: BMC Public Health, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)

Abstract: Molecular diagnostics have revolutionized the diagnosis of multidrug resistant tuberculosis (MDR-TB). Yet in Tanzania we found delay in diagnosis with more than 70% of MDR-TB patients having a history of several previous treatment courses for TB signaling prior opportunities for diagnosis. We aimed to explore patients’ viewpoints and experiences with personal and socio-behavioral obstacles from MDR-TB diagnosis to treatment in an attempt to understand these prior findings. Methods The study was conducted in December 2016 with MDR-TB patients admitted at Kibong’oto Infectious Diseases Hospital. A qualitative approach deploying focus group discussions (FGDs) was used to gather information. Groups were sex aggregated to allow free interaction and to gauge gender specific issues in the social and behavioral contexts. The FGDs explored pathways and factors in the service delivery that may have contributed in the delay in accessing MDR-TB diagnostics and/or treatment. Collected data were coded, categorized and thematically interpreted. Results Forty MDR-TB patients participated in six FGDs. Challenges and barriers contributing to the delay in accessing MDR-TB diagnosis to treatment were as follows: 1) Participants had a different understanding of MDR-TB that led to seeking services outside the conventional health system; 2) Socio-economic adversity made health-seeking behavior difficult and often unproductive; 3) In the health system, challenges included inadequacy of MDR-TB diagnostic centers, lack of knowledge on behalf of health care providers to consider MDR-TB and order appropriate diagnostics; 4) The specimen referral system for early diagnosis of MDR-TB was inefficient. Non-adherence of TB patients to first-line anti-TB drugs prior to MDR-TB diagnosis, given the multitude of barriers discussed, was coupled with both intentional and unintentional non-adherence of health care providers to international standards of TB care. Conclusion Patient-centered strategies bridging communities and the health system are urgently required for optimum MDR-TB control in Tanzania.

Type of Medium: Online Resource

ISSN: 1471-2458

URL: Article

DOI: 10.1186/s12889-020-09774-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2020

detail.hit.zdb_id: 2041338-5

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Application of quantitative second-line drug susceptibility testing at a multidrug-resistant tuberculosis hospital in Tanzania

Mpagama, Stellah G ; Houpt, Eric R ; Stroup, Suzanne ; [et al.]

Springer Science and Business Media LLC ; 2013

In: BMC Infectious Diseases Vol. 13, No. 1 ( 2013-12)

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In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2013-12)

Abstract: Lack of rapid and reliable susceptibility testing for second-line drugs used in the treatment of multidrug-resistant tuberculosis (MDR-TB) may limit treatment success. Methods Mycobacterium tuberculosis isolates from patients referred to Kibong’oto National TB Hospital in Tanzania for second-line TB treatment underwent confirmatory speciation and susceptibility testing. Minimum inhibitory concentration (MIC) testing on MYCOTB Sensititre plates was performed for all drugs available in the second-line formulary. We chose to categorize isolates as borderline susceptible if the MIC was at or one dilution lower than the resistance breakpoint. M. tuberculosis DNA was sequenced for resistance mutations in rpoB (rifampin), inhA (isoniazid, ethionamide), katG (isoniazid), embB (ethambutol), gyrA (fluoroquinolones), rrs (amikacin, kanamycin, capreomycin), eis (kanamycin) and pncA (pyrazinamide). Results Of 22 isolates from patients referred for second-line TB treatment, 13 (59%) were MDR-TB and the remainder had other resistance patterns. MIC testing identified 3 (14%) isolates resistant to ethionamide and another 8 (36%) with borderline susceptibility. No isolate had ofloxacin resistance, but 10 (45%) were borderline susceptible. Amikacin was fully susceptible in 15 (68%) compared to only 11 (50%) for kanamycin. Resistance mutations were absent in gyrA , rrs or eis for all 13 isolates available for sequencing, but pncA mutation resultant in amino acid change or stop codon was present in 6 (46%). Ten (77%) of MDR-TB patients had at least one medication that could have logically been modified based on these results (median 2; maximum 4). The most common modifications were a change from ethioniamide to para-aminosalicylic acid, and the use of higher dose levofloxacin. Conclusions In Tanzania, quantitative second-line susceptibility testing could inform and alter MDR-TB management independent of drug-resistance mutations. Further operational studies are warranted.

Type of Medium: Online Resource

ISSN: 1471-2334

URL: Article

DOI: 10.1186/1471-2334-13-432

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2013

detail.hit.zdb_id: 2041550-3

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Kooperativer Bibliotheksverbund

Berlin Brandenburg