Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children.

BACKGROUND: Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. METHODS: A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional. CONCLUSIONS: These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.

Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children.

BACKGROUND: Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. METHODS: A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional. CONCLUSIONS: These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.

Site of extrapulmonary tuberculosis is associated with HIV infection.

BACKGROUND: In the United States, the proportion of patients with extrapulmonary tuberculosis (EPTB) has increased relative to cases of pulmonary tuberculosis. Patients with central nervous system (CNS)/meningeal and disseminated EPTB and those with human immunodeficiency virus (HIV)/AIDS have increased mortality. The purpose of our study was to determine risk factors associated with particular types of EPTB. METHODS: We retrospectively reviewed 320 cases of EPTB from 1995-2007 at a single urban US public hospital. Medical records were reviewed to determine site of EPTB and patient demographic and clinical characteristics. Multivariable logistic regression analyses were performed to determine independent associations between patient characteristics and site of disease. RESULTS: Patients were predominantly male (67%), African American (82%), and US-born (76%). Mean age was 40 years (range 18-89). The most common sites of EPTB were lymphatic (28%), disseminated (23%), and CNS/meningeal (22%) disease. One hundred fifty-four (48.1%) were HIV-infected, 40% had concomitant pulmonary tuberculosis, and 14.7% died within 12 months of EPTB diagnosis. Multivariable analysis demonstrated that HIV-infected patients were less likely to have pleural (adjusted odds ratio [AOR] 0.3; 95% confidence interval [CI] .2, .6) as site of EPTB disease than HIV-uninfected patients. Among patients with EPTB and HIV-infection, patients with CD4 lymphocyte cell count <100 were more likely to have severe forms of EPTB (CNS/meningeal and/or disseminated) (AOR 1.6; 95% CI, 1.0, 2.4). CONCLUSIONS: Among patients hospitalized with EPTB, patients coinfected with HIV and low CD4 counts were more likely to have CNS/meningeal and disseminated disease. Care for similar patients should include consideration of these forms of EPTB since they carry a high risk of death.

Outcomes and antibiotic use in patients with coronavirus disease 2019 (COVID-19) admitted to an intensive care unit.

Antibiotic overuse is high in patients hospitalized with coronavirus disease 2019 (COVID-19) despite a low documented prevalence of bacterial infections in many studies. In this study evaluating 65 COVID-19 patients in the intensive care unit, empiric broad-spectrum antibiotics were often overutilized with an inertia to de-escalate despite negative culture results.

Vitamin D as adjunctive therapy in refractory pulmonary tuberculosis: a case report.

Vitamin D regulates calcium homeostasis in the body and may play a major role in regulating immune responses to tuberculosis (TB). Pilot studies suggest that vitamin D supplementation may improve outcomes in pulmonary TB (PTB), but clinical evidence using vitamin D in TB treatment is limited. We present a case of vitamin D deficiency in a woman with refractory drug-susceptible PTB. Antituberculous therapy and the correction of vitamin D deficiency resulted in clinical and microbiologic improvement at month 13 of her treatment. The basis for vitamin D/TB interactions and a brief literature review are discussed. Data from controlled trials are needed to evaluate the efficacy of vitamin D as adjunctive TB therapy.

Tuberculosis Mortality in the United States: Epidemiology and Prevention Opportunities.

Rationale: More information on risk factors for death from tuberculosis in the United States could help reduce the tuberculosis mortality rate, which has remained steady for more than a decade.Objective: To identify risk factors for tuberculosis-related death in adults.Methods: We performed a retrospective study of 1,304 adults with tuberculosis who died before treatment completion and 1,039 frequency-matched control subjects who completed tuberculosis treatment in 2005 to 2006 in 13 states reporting 65% of U.S. tuberculosis cases. We used in-depth record abstractions and a standard algorithm to classify deaths in persons with tuberculosis as tuberculosis-related or not. We then compared these classifications to causes of death as coded in death certificates. We used multivariable logistic regression to calculate adjusted odds ratios for predictors of tuberculosis-related death among adults compared with those who completed tuberculosis treatment.Results: Of 1,304 adult deaths, 942 (72%) were tuberculosis related, 272 (21%) were not, and 90 (7%) could not be classified. Of 847 tuberculosis-related deaths with death certificates available, 378 (45%) did not list tuberculosis as a cause of death. Adjusting for known risks, we identified new risks for tuberculosis-related death during treatment: absence of pyrazinamide in the initial regimen (adjusted odds ratio, 3.4; 95% confidence interval, 1.9-6.0); immunosuppressive medications (adjusted odds ratio, 2.5; 95% confidence interval, 1.1-5.6); incomplete tuberculosis diagnostic evaluation (adjusted odds ratio, 2.2; 95% confidence interval, 1.5-3.3), and an alternative nontuberculosis diagnosis before tuberculosis diagnosis (adjusted odds ratio, 1.6; 95% confidence interval, 1.2-2.2).Conclusions: Most persons who died with tuberculosis had a tuberculosis-related death. Intensive record review revealed tuberculosis as a cause of death more often than did death certificate diagnoses. New tools, such as a tuberculosis mortality risk score based on our study findings, may identify patients with tuberculosis for in-hospital interventions to prevent death.

Musculoskeletal Tuberculosis.

Musculoskeletal tuberculosis (TB) accounts for approximately 10% of all extrapulmonary TB cases in the United States and is the third most common site of extrapulmonary TB after pleural and lymphatic disease. Vertebral involvement (tuberculous spondylitis, or Pott's disease) is the most common type of skeletal TB, accounting for about half of all cases of musculoskeletal TB. The presentation of musculoskeletal TB may be insidious over a long period and the diagnosis may be elusive and delayed, as TB may not be the initial consideration in the differential diagnosis. Concomitant pulmonary involvement may not be present, thus confusing the diagnosis even further. Early diagnosis of bone and joint disease is important to minimize the risk of deformity and enhance outcome. The introduction of newer imaging modalities, including MRI (imaging procedure of choice) and CT, has enhanced the diagnostic evaluation of patients with musculoskeletal TB and for directed biopsies of affected areas of the musculoskeletal system. Obtaining appropriate specimens for culture and other diagnostic tests is essential to establish a definitive diagnosis and recover M. tuberculosis for susceptibility testing. A total of 6 to 9 months of a rifampin-based regimen, like treatment of pulmonary TB, is recommended for the treatment of drug susceptible musculoskeletal disease. Randomized trials of tuberculous spondylitis have demonstrated that such regimens are efficacious. These data and those from the treatment of pulmonary TB have been extrapolated to form the basis of treatment regimen recommendations for other forms of musculoskeletal TB.

Increased efficiency in evaluating patients with suspected tuberculosis by use of a dedicated airborne infection isolation unit.

BACKGROUND: The resurgence of tuberculosis (TB) in the 1980s and early 1990s in the United States was also accompanied by numerous hospital outbreaks of TB and nosocomial transmission to health care workers. OBJECTIVE: To determine whether a dedicated airborne infection isolation (AII) unit improves efficiency in "ruling-out" patients suspected of having pulmonary TB. This is important because, to prevent nosocomial transmission of TB, the number and ratio of patients isolated who are subsequently found to have TB is much higher than those "ruled out" and have TB excluded. METHODS: A prospective cohort study was conducted of all patients 18 years and older admitted to respiratory isolation during 3 separate time periods before and after opening of an 26-bed AII unit in a 1000-bed, public, university-affiliated, innercity hospital. RESULTS: A total of 879 patients were admitted during the 3 study periods. Most were black and males (87%, 72%, respectively). The median age was 42 years, and 70% of patients included in the study were HIV positive. Among patients who "ruled out," ie, TB was excluded by having 3 negative AFB smears of respiratory specimens for TB, there was a significant decrease in time from 5.0 days in period I to 3.3 days in period III (P < .0001). In period III, patients who were admitted to rule out TB in areas outside of the AII unit in other wards of the hospital required a significantly longer period to have TB excluded: 5.9 days compared with 3.5 on the AII unit (P = .0015). CONCLUSION: The decrease in isolation time after the opening of the dedicated AII unit demonstrates that a concerted effort to rule patients out by having nurses and respiratory therapists trained in tuberculosis control is efficacious and efficient and results in significant cost savings.

How many sputum specimens are necessary to diagnose pulmonary tuberculosis?

The definitive diagnosis of pulmonary tuberculosis (PTB) relies on identifying or culturing Mycobacterium tuberculosis from respiratory specimens. National guidelines have recommended obtaining 3 sputum specimens from patients with suspected tuberculosis, but there has been little data on the number of specimens actually needed to support a diagnosis. We retrospectively reviewed all patients diagnosed with PTB at a public inner-city hospital and assessed the sensitivity of the acid-fast bacilli (AFB) smear and the number of smears needed to establish the diagnosis. Between January 1, 1997 and October 1, 2000, 425 patients were diagnosed with culture-proven PTB. Acid-fast bacilli (AFB) smears and cultures were performed on 951 respiratory specimens from 425 patients. The overall sensitivity of a positive AFB smear increased from 67% with 1 sputum collected to 71% and 72%, respectively, with the second and third specimens. The sensitivity of smears from 239 HIV-negative patients was 75%, 79%, and 80% with 1, 2, and 3 smears, respectively, collected compared with 57%, 61%, and 62%, respectively, for 142 HIV-positive patients. In summary, 2 respiratory specimens proved adequate in establishing a diagnosis of tuberculosis, and the third specimen added little additional diagnostic value.

Update on the treatment of tuberculosis and latent tuberculosis infection.

Tuberculosis (TB) has emerged as a global public health epidemic. Despite decreasing numbers of cases in the United States since 1992, TB remains a serious public health problem among certain patient populations and is highly prevalent in many urban areas. The responsibility for prescribing an appropriate drug regimen and ensuring that treatment is completed is assigned to the public health program or the clinician not to the patient. The initial prescribed regimen for the treatment of TB usually consists of 4 drugs: isoniazid, rifampin, pyrazinamide, and ethambutol. The minimum length for the treatment of drug-susceptible TB with a rifampin-based regimen is 6 to 9 months. Providing medications directly to the patient and watching him/her swallow the anti-TB drugs, which is termed directly observed therapy, is recommended for all patients diagnosed with TB and can help ensure higher completion rates, prevent the emergence of drug resistant TB, and enhance TB control. There has been renewed interest in the treatment of those with latent TB infection as a TB-control strategy in the United States for eliminating the large reservoir of individuals at risk for progression to TB. The 2 broad categories of persons who should be tested for latent TB infection are those who are likely to have been recently infected (such as contacts to infectious TB cases) and persons who are at increased risk of progression to TB disease following infection with Mycobacterium tuberculosis (eg, human immunodeficiency virus infection and selected medical conditions; recent immigrants to the United States from high TB-burden countries). The preferred regimen for the treatment of latent TB infection is 9 months of isoniazid. There is now renewed interest in and great need for the development of new drugs to treat TB and latent TB infection.

Increased survival of persons with tuberculosis and human immunodeficiency virus infection, 1991--2000.

To determine factors associated with the occurrence of human immunodeficiency virus (HIV) infection and tuberculosis (TB) disease (HIV-TB) and the associated survival rate, we analyzed patients with HIV-TB at Grady Memorial Hospital, Atlanta, Georgia, from 1991 through 2000. Overall, 644 patients with HIV-TB were seen. The number of HIV-TB cases per year was highest in 1992 (102 cases) and declined to 39 cases in 2000. Over time, patients were more likely to be enrolled in the HIV outpatient clinic (P<.01), but, in 1997, only 21 (51%) of 41 patients were enrolled in HIV-infection care programs and only 9 (22%) of 41 received HAART. The 1-year survival rate for patients with HIV-TB was 58% in 1991, 81% in 1994, and 83% in 1997 (P<.001). The increase in survival for patients with HIV-TB between 1991 and 1994 was likely due to improved TB and HIV therapy. More effective strategies for enrolling and maintaining HIV-TB patients in HIV-infection care programs could further increase survival.

Salmonella meningitis in adults infected with HIV: case report and review of the literature.

We report a case of Salmonella infantis meningitis in a patient infected with HIV who was successfully treated with 4 weeks of therapy and has had no relapses after 12 months of follow-up. Only 10 episodes of Salmonella species meningitis in patients infected with HIV are reported in the literature.

Cost analysis of a nucleic acid amplification test in the diagnosis of pulmonary tuberculosis at an urban hospital with a high prevalence of TB/HIV.

INTRODUCTION: The Centers for Disease Control and Prevention has recommended using a nucleic acid amplification test (NAAT) for diagnosing pulmonary tuberculosis (TB) but there is a lack of data on NAAT cost-effectiveness. METHODS: We conducted a prospective cohort study that included all patients with an AFB smear-positive respiratory specimen at Grady Memorial Hospital in Atlanta, GA, USA between January 2002 and June 2008. We determined the sensitivity, specificity, and positive and negative predictive value of a commercially available and FDA-approved NAAT (amplified MTD, Gen-Probe) compared to the gold standard of culture. A cost analysis was performed and included costs related to laboratory tests, hospital charges, anti-TB medications, and contact investigations. Average cost per patient was calculated under two conditions: (1) using a NAAT on all AFB smear-postive respiratory specimens and (2) not using a NAAT. One-way sensitivity analyses were conducted to determine sensitivity of cost difference to reasonable ranges of model inputs. RESULTS: During a 6 1/2 year study period, there were 1,009 patients with an AFB smear-positive respiratory specimen at our public urban hospital. We found the NAAT to be highly sensitive (99.6%) and specific (99.1%) on AFB smear-positive specimens compared to culture. Overall, the positive predictive value (PPV) of an AFB smear-positive respiratory specimen for culture-confirmed TB was 27%. The PPV of an AFB smear-positive respiratory specimen for culture-confirmed TB was significantly higher for HIV-uninfected persons compared to those who were HIV-seropositive (152/271 [56%] vs. 85/445 [19%]; RR = 2.94, 95% CI 2.36-3.65, p<0.001). The cost savings of using the NAAT was $2,003 per AFB smear-positive case. CONCLUSIONS: Routine use of the NAAT on AFB smear-positive respiratory specimens was highly cost-saving in our setting at a U.S. urban public hospital with a high prevalence of TB and HIV because of the low PPV of an AFB smear for culture-confirmed TB.

Use of a molecular diagnostic test in AFB smear positive tuberculosis suspects greatly reduces time to detection of multidrug resistant tuberculosis.

BACKGROUND: The WHO has recommended the implementation of rapid diagnostic tests to detect and help combat M/XDR tuberculosis (TB). There are limited data on the performance and impact of these tests in field settings. METHODS: The performance of the commercially available Genotype MTBDRplus molecular assay was compared to conventional methods including AFB smear, culture and drug susceptibility testing (DST) using both an absolute concentration method on Löwenstein-Jensen media and broth-based method using the MGIT 960 system. Sputum specimens were obtained from TB suspects in the country of Georgia who received care through the National TB Program. RESULTS: Among 500 AFB smear-positive sputum specimens, 458 (91.6%) had both a positive sputum culture for Mycobacterium tuberculosis and a valid MTBDRplus assay result. The MTBDRplus assay detected isoniazid (INH) resistance directly from the sputum specimen in 159 (89.8%) of 177 specimens and MDR-TB in 109 (95.6%) of 114 specimens compared to conventional methods. There was high agreement between the MTBDRplus assay and conventional DST results in detecting MDR-TB (kappa = 0.95, p<0.01). The most prevalent INH resistance mutation was S315T (78%) in the katG codon and the most common rifampicin resistance mutation was S531L (68%) in the rpoB codon. Among 13 specimens from TB suspects with negative sputum cultures, 7 had a positive MTBDRplus assay (3 with MDR-TB). The time to detection of MDR-TB was significantly less using the MTBDRplus assay (4.2 days) compared to the use of standard phenotypic tests (67.3 days with solid media and 21.6 days with broth-based media). CONCLUSIONS: Compared to conventional methods, the MTBDRplus assay had high accuracy and significantly reduced time to detection of MDR-TB in an area with high MDR-TB prevalence. The use of rapid molecular diagnostic tests for TB and drug resistance should increase the proportion of patients promptly placed on appropriate therapy.

Acute forms of tuberculosis in adults.

Although typically considered a chronic disease, tuberculosis (TB) has protean acute manifestations, the major forms of which are reviewed in this article. The pathogenesis of acute TB, although still incompletely understood, may be related to both epidemiologic and genetic host factors. Miliary TB manifests as a nonspecific clinical syndrome with a high mortality rate. The most well-known form of acute TB is meningitis, characterized by fever, nuchal rigidity, and a lymphocytic pleocytosis of the cerebrospinal fluid. Acute abdominal TB may present with obstruction or less commonly as perforated viscus or peritonitis. Critically ill patients may have acute respiratory distress syndrome, shock, or disseminated intravascular coagulopathy. The spectrum of disease makes diagnosis of acute TB difficult unless clinical suspicion of disease is high, but the high mortality mandates its consideration. Early initiation of therapy is crucial to optimize clinical outcome.

Etiology of neonatal blood stream infections in Tbilisi, Republic of Georgia.

BACKGROUND: Neonatal blood stream infections (BSI) are a major cause of morbidity and mortality in developing countries. It is crucial to continuously monitor the local epidemiology of neonatal BSI to detect any changes in patterns of infection and susceptibility to various antibiotics. OBJECTIVES: To examine the etiology of BSI in two neonatal intensive care units (NICUs) in the Republic of Georgia, a resource-poor country, and to determine antibiotic susceptibility of the isolated organisms. METHODS: A cross-sectional study of all septic infants was conducted in the NICUs of two pediatric hospitals in Tbilisi between September 2003 and September 2004. RESULTS: A total of 200 infants with clinical signs of sepsis were admitted to two NICUs. Of these, 126 (63%) had confirmed bacteremia. The mortality rate was 34%. A total of 98 (78%) of 126 recovered isolates were Gram-negative organisms and 28 (22%) were Gram-positive. Klebsiella pneumoniae was the most common pathogen, accounting for 36 (29%) of 126 isolates, followed by Enterobacter cloacae accounting for 19 (15%) and Staphylococcus aureus accounting for 15 (12%). The Gram-negative organisms showed a high degree of resistance to commonly used antibiotics such as ampicillin and amoxicillin/clavulanate, and comparatively low resistance to amikacin, ciprofloxacin, carbapenems, and gentamicin; 40% of S. aureus isolates were methicillin-resistant (MRSA). In multivariate analysis only umbilical discharge was a significant risk factor for having a positive blood culture at admission to NICU (prevalence ratio = 2.25, 95% confidence interval 1.82-2.77). CONCLUSIONS: Neonatal BSI was mainly caused by Gram-negative organisms, which are developing resistance to commonly used antibiotics. Understanding the local epidemiology of neonatal BSI can lead to the development of better medical practices, especially more appropriate choices for empiric antibiotic therapy, and may contribute to improvement of infection control practices.