Marcos C. Schechter

Time to Sputum Culture Conversion and Treatment Outcomes Among Patients with Isoniazid-Resistant Tuberculosis in Atlanta, Georgia

Background Although isoniazid-resistant tuberculosis is more common than multidrug-resistant tuberculosis, it has been much less studied. We examined the impact of isoniazid resistance and treatment regimen, including use of a fluoroquinolone, on clinical outcomes. Methods A retrospective cohort study among patients with sputum culture-positive tuberculosis was performed. Early fluoroquinolone (FQ) use was defined as receiving ≥5 doses during the first month of treatment. The primary outcome was time to sputum culture conversion (tSCC). A multivariate proportional hazards model was used to determine the association of isoniazid resistance with tSCC. Results Among 236 patients with pulmonary tuberculosis, 59 (25%) had isoniazid resistance. The median tSCC was similar for isoniazid-resistant and -susceptible cases (35 vs 29 days; P = .39), and isoniazid resistance was not associated with tSCC in multivariate analysis (adjusted hazard ratio = 0.83; 95% confidence interval [CI], .59-1.17). Early FQ use was higher in isoniazid-resistant than -susceptible cases (20% vs 10%; P = .05); however, it was not significantly associated with tSCC in univariate analysis (hazard ratio = 1.48; 95% CI, .95-2.28). Patients with isoniazid-resistant tuberculosis were treated with regimens containing rifampin, pyrazinamide, and ethambutol +/- a FQ for a median of 9.7 months. Overall, 191 (83%) patients were cured. There was no difference in initial treatment outcomes; however, all cases of acquired-drug resistance (n = 1) and recurrence (n = 3) occurred among patients with isoniazid-resistant tuberculosis. Conclusions There was no significant association with isoniazid resistance and tSCC or initial treatment outcomes. Although patients with isoniazid-resistant tuberculosis had a high cure rate, the cases of recurrence and acquired drug resistance are concerning and highlight the need for longer-term follow-up studies.

Bilateral Central Retinal Artery Occlusion Associated With Herpes Simplex Virus–Associated Acute Retinal Necrosis and Meningitis: Case Report and Literature Review

A 60-year-old woman with a history of recurrent headaches and blurred vision presented with bilateral optic disc edema. Optic neuritis was suspected, and intravenous methylprednisonlone was administered. Her vision declined to hand motions in both eyes, and subsequent evaluation revealed bilateral acute retinal necrosis with bilateral central retinal artery occlusions (CRAO). Aqueous humor polymerase chain reaction analysis was positive for herpes simplex virus (HSV), establishing a diagnosis of HSV-associated bilateral acute retinal necrosis (ARN) and meningitis. CRAO has rarely been reported in association with ARN, and a fulminant course with bilateral CRAO in association with ARN has not been previously reported. This case emphasizes the importance of careful peripheral examination in patients with presumptive optic neuritis, judicious use of systemic corticosteroid in this context, and the retinal vaso-obliterative findings that may be observed in the pathogenesis of ARN.

Unusual presentation of chikungunya virus infection with concomintant erysipelas in a returning traveler from the Caribbean: a case report.

Chikungunya fever is a mosquito-borne febrile illness caused by Chikungunya virus (CHIKV), an alphavirus from the Togaviridae family. It is transmitted by primarily Aedes aegytpi and Aedes albopictus mosquitos [1]. Once of little importance in the Americas, local transmission was identified in the Caribbean in late 2013. More than 1000 travelers returning to the continental United States have been diagnosed with CHIKV. More importantly, there have been 9 documented cases of autochthonous disease in Florida as of September 16, 2014 [2].

Challenges Across the HIV Care Continuum for Patients With HIV/TB Co-infection in Atlanta, GA

Abstract Background Antiretroviral therapy (ART) for persons with HIV infection prevents tuberculosis (TB) disease. Additionally, sequential ART after initiation of TB treatment improves outcomes. We examined ART use, retention in care, and viral suppression (VS) before, during, and 3 years following TB treatment for an inner-city cohort in the United States. Methods Retrospective cohort study among persons treated for culture-confirmed TB between 2008 and 2015 at an inner-city hospital. Results Among 274 persons with culture-confirmed TB, 96 (35%) had HIV co-infection, including 23 (24%) new HIV diagnoses and 73 (76%) previous diagnoses. Among those with known HIV prior to TB, the median time of known HIV was 6 years, and only 10 (14%) were on ART at the time of TB diagnosis. The median CD4 at TB diagnosis was 87 cells/uL. Seventy-four (81%) patients received ART during treatment for TB, and 47 (52%) has VS at the end of TB treatment. Only 32% of patients had continuous VS 3 years after completing TB treatment. There were 3 TB recurrences and 3 deaths post–TB treatment; none of these patients had retention or VS after TB treatment. Conclusions Among persons with active TB co-infected with HIV, we found that the majority had known HIV and were not on ART prior to TB diagnosis, and retention in care and VS post–TB treatment were very low. Strengthening the HIV care continuum is needed to improve HIV outcomes and further reduce rates of active TB/HIV co-infection in our and similar settings.

Developing an Assessment Framework for Essential Internal Medicine Subspecialty Topics

Background Assessing residents by direct observation is the preferred assessment method for infrequently encountered subspecialty topics, but this is logistically challenging. Objective We developed an assessment framework for internal medicine (IM) residents in subspecialty topics, using tuberculosis diagnosis for proof of concept. Methods We used a 4-step process at 8 academic medical centers that entailed (1) creating a 10-item knowledge assessment tool; (2) pilot testing on a sample of 129 IM residents and infectious disease fellow volunteers to evaluate validity evidence; (3) implementing the final tool among 886 resident volunteers; and (4) assessing outcomes via retrospective chart review. Outcomes included tool score, item performance, and rates of obtaining recommended diagnostics. Results Following tool development, 10 infectious disease experts provided content validity. Pilot testing showed higher mean scores for fellows compared with residents (7 [SD = 1.8] versus 3.8 [SD = 1.7], respectively, P < .001) and a satisfactory Kuder-Richardson Formula 20 (0.72). Implementation of the tool revealed a 14-minute (SD = 2.0) mean completion time, 61% (541 of 886) response rate, 4.4 (SD = 1.6) mean score, and ≤ 57% correct response rate for 9 of 10 items. On chart review (n = 343), the rate of obtaining each recommended test was ≤ 43% (113 of 261), except for chest x-rays (96%, 328 of 343). Conclusions Our assessment framework revealed knowledge and practice gaps in tuberculosis diagnosis in IM residents. Adopting this approach may help ensure assessment is not limited to frequently encountered topics.

Neutrophil extracellular trap (NET) levels in human plasma are associated with active TB

Neutrophils are increasingly associated with tuberculosis (TB) disease. Neutrophil extracellular traps (NETs), which are released by neutrophils as a host antimicrobial defense mechanism, are also associated with tissue damage. However, a link between NET levels and TB disease has not been studied. Here we investigate plasma NETs levels in patients with active pulmonary tuberculosis using an ELISA assay that is suitable for high-throughput processing. We show that plasma NETs levels at baseline correlated with disease severity and decreased with antibiotic therapy. Our study demonstrates the biologic plausibility of measuring NETs in plasma samples from patients with TB.

Isoniazid Monoresistance and Rate of Culture Conversion among Patients in the State of Georgia with Confirmed Tuberculosis, 2009–2014

Rationale: Isoniazid‐monoresistant tuberculosis (INH‐monoresistant TB) is the most common drug‐resistant TB type in the United States; however, its impact on TB treatment outcomes is not clear. Objectives: This study aims to understand 1) factors associated with INH‐monoresistant TB and 2) the association between INH monoresistance and response to TB treatment. Methods: We studied all patients with TB (age, ≥15 yr) reported to the Georgia State Electronic Notifiable Disease Surveillance System (SENDSS) from 2009 to 2014. INH‐monoresistant TB was defined as a Mycobacterium tuberculosis isolate resistant to isoniazid only. Time to sputum culture conversion was defined as the time (measured in days) from TB treatment initiation to the date of the first consistently negative culture result reported to the SENDSS. Logistic regression and Cox proportional hazard models were used to estimate the odds and hazard rate of sputum culture conversion, all‐cause mortality, and poor TB outcome among patients with INH‐monoresistant TB. Results: Among 1,141 culture‐confirmed patients with available drug susceptibility testing results, 998 (87.5%) were susceptible to TB first‐line drugs, and 143 (12.5%) were patients with INH‐monoresistant TB. In multivariable analysis, male sex (adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 1.01‐2.67) and homelessness (aOR, 5.55; 95% CI, 3.38‐9.17) were associated with higher odds of INH‐monoresistant TB. In the same multivariable model, older age (≥65 yr old) (aOR, 0.21; 95% CI, 0.07‐0.55) and miliary disease (aOR, 0.19; 95% CI, 0.01‐0.96) were associated with lower odds of INH‐monoresistant TB. Among 1,116 patients with pulmonary TB, the median time to sputum culture conversion was 30 days (interquartile range, 13‐58). The rate of culture conversion was similar among patients with and without INH monoresistance (adjusted cause‐specific hazard ratio, 1.15; 95% CI, 0.95‐1.40). INH‐monoresistant TB was not significantly associated with poor TB treatment outcomes (aOR, 1.61; 95% CI, 0.67‐3.70) or mortality during TB treatment (aOR, 1.72; 95% CI, 0.58‐4.94). Conclusions: Our findings suggest that compared with drug‐susceptible TB, patients in Georgia with INH‐monoresistant TB have a similar response to TB treatment including culture conversion rate, final TB treatment outcome, and all‐cause mortality.

Internal medicine residents' knowledge and practice of pulmonary tuberculosis diagnosis

Abstract Background Internal medicine physicians are often the first providers to encounter patients with a new diagnosis of tuberculosis. Given the public health risks of missed tuberculosis cases, assessing internal medicine residents’ ability to diagnose tuberculosis is important. Methods Internal medicine resident knowledge and practice patterns in pulmonary tuberculosis diagnosis at 7 academic hospitals were assessed utilizing (a) a 10-item validated pulmonary tuberculosis diagnosis assessment tool and (b) a retrospective chart review of 343 patients who underwent a pulmonary tuberculosis evaluation while admitted to a resident-staffed internal medicine or infectious disease service. Our primary outcomes were the mean score and percentage of correct responses per assessment tool question, and the percentage of patients who had Centers for Disease Control and Prevention–recommended tuberculosis diagnostic tests obtained. Results Of the 886 residents who received the assessment, 541 responded, yielding a response rate of 61%. The mean score on the assessment tool (SD) was 4.4 (1.6), and the correct response rate was 57% (311/541) or less on 9 of 10 questions. On chart review, each recommended test was obtained for ≤43% (148/343) of patients, other than chest x-ray (328/343; 96%). A nucleic acid amplification test was obtained for 18% (62/343) of patients, whereas 24% (83/343) had only 1 respiratory sample obtained. Twenty patients were diagnosed with tuberculosis. Conclusions Significant knowledge and practice gaps exist in internal medicine residents’ abilities to diagnose tuberculosis. As residents represent the future providers who will be evaluating patients with possible tuberculosis, such deficiencies must be addressed.