Increased Incidence of Multidrug-Resistant Tuberculosis in Diabetic Patients on the Bellevue Chest Service, 1987 to 1997

doi:10.1378/chest.120.5.1514

Chest

Volume 120, Issue 5, November 2001, Pages 1514-1519

https://doi.org/10.1378/chest.120.5.1514 Get rights and content

Study objectives

To investigate the characteristics of tuberculosis infection in diabetic patients at Bellevue Hospital.

Design

We conducted a case-control study retrospectively reviewing the records of patients at Bellevue Hospital Center from 1987 to 1997 with a discharge diagnosis of tuberculosis and diabetes mellitus.

Setting

Bellevue Hospital Center is a 1,200-bed, inner-city municipal hospital located in the Lower East Side of New York City.

Patients

Fifty-three identified patients had verified tuberculosis infection and diabetes; of these, 50 charts were available for review. One hundred five control cases were selected from nondiabetic patients with a discharge diagnosis of tuberculosis during the same time period.

Measurements and results

Thirty-six percent (18 cases) of the patients with diabetes and tuberculosis had multidrug-resistant tuberculosis (MDR-TB) compared to only 10% (10 cases) in the control group (p < 0.01) Controlling for homelessness, HIV status, and directly observed therapy, the relative risk of MDR-TB was calculated to be 8.6 (confidence interval, 3.1 to 23.6) in the diabetic group compared to the control group.

Conclusions

There was a significant association between diabetes and MDR-TB. Diabetes continues to be a risk factor for tuberculosis and was associated with MDR-TB in our patients.

Section snippets

Materials and Methods

Charts of patients from the time period from 1987 to 1997 with the combined discharge diagnosis of tuberculosis and diabetes mellitus were reviewed for the following information: demographic data, details of tuberculosis disease with site of disease, date of initial diagnosis and drug sensitivity patterns, prior history of tuberculosis disease, purified protein derivative status, HIV status (as determined by enzyme-linked immunosorbent assay and Western blot), CD4 count, details of diabetes

Results

Sixty-nine patients were identified through the review of discharge diagnoses at Bellevue Hospital during the 11-year period from 1987 to 1997 as having both tuberculosis and diabetes mellitus. Sixteen of these cases were considered noncountable by the Department of Health because the sputum cultures either grew nontuberculous acid-fast bacilli or failed to grow and treatment was discontinued. Of the 53 confirmed cases, 50 had medical records that were available for review; three charts were

Discussion

Our study revealed that the proportion of cases of MDR-TB was significantly higher in patients with coexisting diabetes mellitus. After controlling for homelessness and HIV status, both risk factors for the development of drug-resistant tuberculosis, we found that diabetic patients were at increased risk for MDR-TB, with an adjusted odds ratio of 5.3 (CI, 1.9 to 14.6). Frieden and colleagues⁶ reported the emergence of drug-resistant tuberculosis in New York City in 1991. They reported that the

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Cited by (124)

Drug resistance of previously treated tuberculosis patients with diabetes mellitus in Shandong, China
2020, Respiratory Medicine
Citation Excerpt :
The global burden of TB-DM overlap is high, with a prevalence of 16% globally, 24% in North America, 23% in Oceania, 17% in Asia, 11% in South America, 7% in Africa, and 6% in Europe [10]. Recent years, there are a growing number of researches centred on the risk of active or latent tuberculosis infection among diabetes patients, and treatment outcomes or rate of smear conversion among TB-DM patients (defined as tuberculosis cases with diabetes) [7,10,11]. However, few previous study [5,7,8] had focused on acquired drug resistance profiles and clinical characteristics among retreated TB-DM patients, most of which were conducted among newly diagnosed TB cases.
Although the association between diabetes mellitus (DM) and tuberculosis (TB) has been well-documented for centuries, evidence of the link between diabetes and drug resistance among previously treated TB patients remains limited and inconsistent.
An observational study was performed that involved 1791 retreated TB-no DM patients (refers to TB cases without diabetes) and 93 retreated TB-DM patients (refers to TB cases with diabetes) in Shandong, China from 2004 to 2017. Baseline data including demographic and clinical characteristics, drug susceptibility test (DST) results, and diabetes status were collected. Categorical baseline characteristics were compared by Fisher's exact or Pearson Chi-square test. Univariable analysis and multivariable logistic models were used to estimate the association between diabetes and different drug resistance profiles.
Retreated TB-DM patients have a higher rate of drug resistance than TB-no DM patients (34.41% vs 25.00%, P < 0.01). Diabetes co-morbidity was significantly associated with any drug-resistant tuberculosis (DR-TB, odds ratio (OR):1.56, 95% confidence interval (CI): 1.01–2.43), multidrug resistant tuberculosis (MDR-TB, OR: 2.48, 95%CI:1.39–4.41; adjusted OR (aOR):2.94, 95%CI:1.57–5.48), isoniazid-related resistance (OR:1.71, 95%CI:1.04–2.81), rifampin-related resistance (OR:2.56, 0.54, 95%CI: 1.54–4.26; aOR:2.69, 95%CI:1.524–4.74), isoniazid + rifampin resistance (OR: 3.55, 95%CI:1.33–9.44; aOR:4.13, 95%CI:1.46–11.66), any resistance to isoniazid + streptomycin (OR:2.34, 95%CI:1.41–3.89; aOR:2.22, 95%CI:1.26–3.94), and any resistance to rifampin + isoniazid (OR:2.48, 95%CI:1.39–4.41; aOR:2.94, 95%CI: 1.57–5.48), compared with pan susceptible TB cases, P < 0.05.
The risk of acquired drug resistance increased significantly among retreated TB-DM patients compared with retreated TB-no DM patients, underlining the necessity of more interventions during the clinical management of TB-DM cases.
Diabetes is Associated with Severe Adverse Events in Multidrug-Resistant Tuberculosis
2017, Archivos de Bronconeumologia
La diabetes mellitus (DM), una enfermedad muy frecuente en México, es un factor de riesgo bien conocido para el desarrollo de tuberculosis (TB). Sin embargo, se desconoce en qué medida la DM predispone al desarrollo de reacciones adversas (RA) a los fármacos anti-tuberculosis y/o si predispone a un peor resultado en pacientes con pacientes con TB multirresistente (TB-MR) y TB extremadamente resistente (TB-XR). El objetivo principal de este estudio fue describir los resultados del tratamiento anti-tuberculosis, el impacto de la DM y la prevalencia de RA en una cohorte de pacientes con TB pulmonar MR/XR tratados en el centro de referencia nacional para TB, en la Ciudad de México.
Entre 2010 y 2015 se incluyeron 90 pacientes —73 con TB-MR (81,1%), 11 con TB pre-XR (12,2%) y 6 (6,7%) con TB-XR—, 49 (54,4%) de los cuales tenían DM y 3 con co-infección por el virus de la inmunodeficiencia humana (VIH) (3,3%). El diagnóstico se realizó mediante cultivo y pruebas de fármaco-sensibilidad (PFS) en el 98% de los pacientes y mediante prueba molecular en un caso. La presencia de DM se asoció con un mayor riesgo de RA graves, tales como nefrotoxicidad (odds ratio [OR] = 6,5; intervalo de confianza del 95% [IC 95%]: 1,9-21,8) e hipotiroidismo (OR = 8,8; IC 95%: 1,8-54,2), aunque no con peor resultado del tratamiento.
Nuestros datos sugieren que la DM no tiene un impacto sobre los resultados del tratamiento anti-tuberculosis de segunda línea, pero los pacientes con DM tienen mayor riesgo de presentar RA graves secundarias al tratamiento, tales como nefrotoxicidad e hipotiroidismo.
Diabetes mellitus (DM), a very common disease in Mexico, is a well-known risk factor for tuberculosis (TB). However, it is not known by which extent DM predisposes to adverse events (AE) to anti-TB drugs and/or to worse outcomes in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB). The main objective of this study was to describe the outcomes of TB treatment, the impact of DM and the prevalence of AE in a cohort of patients with MDR-/XDR pulmonary TB treated at the national TB referral centre in Mexico City.
Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (12.2%) and 6 (6.7%) with XDR-TB, including 49 (54.4%) with DM, and 3 with Human Immunodeficiency Virus (HIV) co-infection (3.3%). In 98% of patients, diagnosis was made by culture and drug susceptibility testing, while in a single case the diagnosis was made by a molecular test. The presence of DM was associated with an increased risk of serious drug-related AEs, such as nephrotoxicity (Odds Ratio [OR] = 6.5; 95% Confidence Interval [95% CI]: 1.9-21.8) and hypothyroidism (OR = 8.8; 95% CI: 1.8-54.2), but not for a worse outcome.
Our data suggest that DM does not impact second-line TB treatment outcomes, but patients with DM have a higher risk of developing serious AEs to drug-resistant TB treatment, such as nephrotoxicity and hypothyroidism.
The effect size of type 2 diabetes mellitus on tuberculosis drug resistance and adverse treatment outcomes
2017, Tuberculosis
To evaluate the effect size of type 2 diabetes mellitus (T2DM) on tuberculosis (TB) treatment outcomes and multi drug resistance (MDR).
A cohort with 507 individuals with diagnosed TB included 183 with coexistence of T2DM and TB (TB-T2DM). Participants were identified at the time of TB diagnosis and followed during the course of TB treatment. Then we computed relative risks and adjustments by Cox proportional hazards for outcome variables (drug resistance, death, relapse, treatment failure), and the size of their effect as Cohen's-d.
Patients with TB-T2DM were more likely to remain positive for acid-fast bacilli after two months of anti-TB treatment RR = [2.01 (95% CI: 1.3, 3.1)], to have drug resistant (DR) [OR 3.5 (95% CI: 1.8, 6.7)] and multi-drug resistant (MDR) TB [OR 3.5 (95% CI: 1.8, 7.1)]. The Cohen's-d for DR or MDR in T2DM was 0.69 when compared with non-DM subjects. The T2DM patients had higher odds of resistance to isoniazid (OR 3.9, 95% CI: 2.01, 7.9), rifampicin (OR 3.4, 95% CI: 1.6, 7.2) and pyrazinamide (OR 9.4, 95% CI: 2.8, 25.6), and their effect sizes were ≥0.67. Patients with TB-T2DM (versus no DM) were more likely to present with MDR TB (HR 3.1; 95% CI: 1.7, 5.8; p < 0.001), treatment failure (HR 2.04; 95% CI: 1.07, 3.8; p = 0.02) and relapse (HR 1.86; 95% CI: 1.09, 3.1; p = 0.02), with effect size ≥0.34.
T2DM showed a substantial contribution to the presence of DR or MDR-TB and to adverse clinical outcomes during and after TB treatment. Our findings support the importance for routine screening of T2DM among newly-diagnosed TB patients in order to stratify them for immediate DR assessment, and highlight the need for clinical trials to evaluate variations to the standard TB treatment in TB-T2DM to prevent adverse treatment outcomes.
Prognostic factors of treatment among patients with multidrug-resistant tuberculosis in Egypt
2016, Journal of the Formosan Medical Association
Citation Excerpt :
The relationship between diabetes mellitus and MDR-TB is a point of controversy. While some studies could not find such a relation,21–23 others observed an increased risk of MDR-TB, ranging from 2.1 to 8.8 times, and a relapse with resistant strains among diabetics.24–27 On the other hand, an increased risk of poor treatment outcome of MDR-TB was documented among diabetics.5,28–30
Multidrug-resistant tuberculosis (MDR-TB) represents 5% of TB cases globally. In Egypt, it represents 11.4% of TB cases (2.2% of new and 38.2% of previously treated). Our objectives were to evaluate the treatment outcomes and determine the associated prognostic factors among the first national treatment cohort of MDR-TB from 2006 to 2010.
All patients diagnosed with MDR-TB from July 2006 to December 2010 who were admitted to Abbassia Chest Hospital, the first Egyptian national center established for MDR-TB treatment, were included. They were followed up clinically, radiologically, and bacteriologically by sputum smear, culture, and drug-susceptibility testing at regular intervals. Individualized treatment regimens were prescribed according to each patient's drug-susceptibility testing and the drug treatment history. Patients received at least five effective drugs. Outcome rates, and crude and adjusted odds ratios of unsuccessful outcomes were calculated.
The number of bacteriologically proven MDR-TB patients was 228, of which 225 were pulmonary cases. Half of the cases showed moderate or extensive lung lesions, and 15.8% were diabetics. A total of 158 (119 cured and 39 completed treatment) patients achieved successful outcome (69.3%), 16 (7.1%) failed treatment, 27 (11.8%) were lost to follow up, and 27 (11.8%) died. Predictors of unsuccessful outcome were delay in sputum culture conversion to 2 months or more, moderate or extensive lung lesions, and a history of diabetes.
A treatment success rate of approximately 69% was achieved with the first national treatment cohort of MDR-TB under the Egyptian program. Predictors of unsuccessful treatment were delayed culture conversion, moderate or extensive lung affection, and diabetes.
Adherence interventions and outcomes of tuberculosis treatment: A systematic review and meta-analysis of trials and observational studies
2018, PLoS Medicine
Incomplete adherence to tuberculosis (TB) treatment increases the risk of delayed culture conversion with continued transmission in the community, as well as treatment failure, relapse, and development or amplification of drug resistance. We conducted a systematic review and meta-analysis of adherence interventions, including directly observed therapy (DOT), to determine which approaches lead to improved TB treatment outcomes.
We systematically reviewed Medline as well as the references of published review articles for relevant studies of adherence to multidrug treatment of both drug-susceptible and drug-resistant TB through February 3, 2018. We included randomized controlled trials (RCTs) as well as prospective and retrospective cohort studies (CSs) with an internal or external control group that evaluated any adherence intervention and conducted a meta-analysis of their impact on TB treatment outcomes. Our search identified 7,729 articles, of which 129 met the inclusion criteria for quantitative analysis. Seven adherence categories were identified, including DOT offered by different providers and at various locations, reminders and tracers, incentives and enablers, patient education, digital technologies (short message services [SMSs] via mobile phones and video-observed therapy [VOT]), staff education, and combinations of these interventions. When compared with DOT alone, self-administered therapy (SAT) was associated with lower rates of treatment success (CS: risk ratio [RR] 0.81, 95% CI 0.73–0.89; RCT: RR 0.94, 95% CI 0.89–0.98), adherence (CS: RR 0.83, 95% CI 0.75–0.93), and sputum smear conversion (RCT: RR 0.92, 95% CI 0.87–0.98) as well as higher rates of development of drug resistance (CS: RR 4.19, 95% CI 2.34–7.49). When compared to DOT provided by healthcare providers, DOT provided by family members was associated with a lower rate of adherence (CS: RR 0.86, 95% CI 0.79–0.94). DOT delivery in the community versus at the clinic was associated with a higher rate of treatment success (CS: RR 1.08, 95% CI 1.01–1.15) and sputum conversion at the end of two months (CS: RR 1.05, 95% CI 1.02–1.08) as well as lower rates of treatment failure (CS: RR 0.56, 95% CI 0.33–0.95) and loss to follow-up (CS: RR 0.63, 95% CI 0.40–0.98). Medication monitors improved adherence and treatment success and VOT was comparable with DOT. SMS reminders led to a higher treatment completion rate in one RCT and were associated with higher rates of cure and sputum conversion when used in combination with medication monitors. TB treatment outcomes improved when patient education, healthcare provider education, incentives and enablers, psychological interventions, reminders and tracers, or mobile digital technologies were employed. Our findings are limited by the heterogeneity of the included studies and lack of standardized research methodology on adherence interventions.
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In this systematic review and meta-analysis, Payam Nahid and colleagues investigate results from trials and observational studies to identify methods for encouraging patients to complete tuberculosis treatment that are associated with improved TB outcomes.
Global burden of MDR-TB and XDR-TB attributable to high fasting plasma glucose from 1990 to 2019: a retrospective analysis based on the global burden of disease study 2019
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: This research was supported in part by a General Clinical Research Center grant from the National Institutes of Health, National Center for Research Resources (M01RR00096) awarded to the New York University School of Medicine, New York, NY.

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Chest

Clinical InvestigationsTUBERCULOSISIncreased Incidence of Multidrug-Resistant Tuberculosis in Diabetic Patients on the Bellevue Chest Service, 1987 to 1997

Study objectives

Design

Setting

Patients

Measurements and results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Chest

Chest

Endemic tuberculosis among homeless men in New York City

Arch Intern Med

Outcome of MDR-TB patients, 1983–1993: prolonged survival with appropriate therapy

Am J Respir Crit Care Med

Screening for infection and disease as a tuberculosis control measure among indigents in New York City, 1994–1997

Int J Tuberc Lung Dis

Incidence of pulmonary tuberculosis among diabetics

Tuberc Lung Dis

Clinical Investigations
TUBERCULOSIS
Increased Incidence of Multidrug-Resistant Tuberculosis in Diabetic Patients on the Bellevue Chest Service, 1987 to 1997