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1.  Site of Extrapulmonary Tuberculosis is Associated with HIV Infection 
The site of extrapulmonary tuberculosis infection has a known effect on mortality. Authors use a large clinical case series to identify previously unconfirmed risk factors that are associated with site of extrapulmonary tuberculosis 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.
doi:10.1093/cid/cis303
PMCID: PMC3493181  PMID: 22423123
2.  Use of a Molecular Diagnostic Test in AFB Smear Positive Tuberculosis Suspects Greatly Reduces Time to Detection of Multidrug Resistant Tuberculosis 
PLoS ONE  2012;7(2):e31563.
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.
doi:10.1371/journal.pone.0031563
PMCID: PMC3276512  PMID: 22347495
3.  Vitamin D as Adjunctive Therapy in Refractory Pulmonary Tuberculosis: A Case Report 
Southern medical journal  2009;102(6):649-652.
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.
doi:10.1097/SMJ.0b013e3181a5d37e
PMCID: PMC2892733  PMID: 19434014
immunity; treatment; tuberculosis; vitamin D
4.  Etiology of Neonatal Blood Stream Infections in Tbilisi, Republic of Georgia 
Introduction
Neonatal blood stream infections (BSI) are 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.
Objective
To examine the etiology of BSI in two neonatal intensive care units (NICU) in the Republic of Georgia, a resource-poor country, and to determine antibiotic susceptibility of the isolated organisms.
Methods
Cross-sectional study among all septic infants was conducted in NICU of two pediatric hospitals in Tbilisi between 09/2003-09/2004.
Results
A total of 200 infants with clinical signs of sepsis were admitted in two NICUs. Of these, 126 (63%) had confirmed bacteremia. 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 – 19 (15%), and S. aureus – 15 (12%). The gram-negative organisms showed high degree of resistance to commonly used antibiotics such as ampicillin, 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 positive blood culture at admission to NICU (PR=2.25, 95% CI 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.
doi:10.1016/j.ijid.2008.08.020
PMCID: PMC2695829  PMID: 19058989
blood stream infections; Republic of Georgia; neonatal
6.  High Mortality among Patients with Positive Blood Cultures at a Children's Hospital in Tbilisi, Georgia 
Background
The etiology and outcomes of blood stream infections (BSI) among pediatric patients is not well described in resource-limited countries including Georgia.
Methods
Patients with positive blood cultures at the largest pediatric hospital in the country of Georgia were identified by review of medical and laboratory records for patients who had blood cultures obtained between 01/2004-06/2006.
Results
Of 1,693 blood cultures obtained during the study period, 338 (20%) were positive; 299 were included in our analysis. The median age was 14 days (range 2 days -14 years) and 178 (60%) were male; 53% of patients with a positive culture were admitted to Neonatal Intensive Care Unit (NICU). Gram-negative bacilli (GNB) were representing 165 (55%) of 299 cultures. Further speciation of 135 (82%) of 165 GNR was not possible because of lack of laboratory capacity. Overall mortality was 30% (90 of 299). Among the 90 children who died, 80 (89%) were neonates and 68 (76%) had BSI caused by Gram-negative organism. In multivariate analysis, independent risk factors for in-hospital mortality included age <30 days (OR=4.00, 95% CI 1.89-8.46) and having a positive blood culture for a Gram-negative BSI (OR=2.38, 95% CI 1.32-4.29).
Conclusions
A high mortality was seen among children, particularly neonates, with positive blood cultures at the largest pediatric hospital in Georgia. Because of limited laboratory capacity microbiological identification of common organisms known to cause BSI in children was not possible and susceptibility testing was not performed. Improving the infrastructure of diagnostic microbiology laboratories in resource limited countries is critical in order to improve patient care and clinical outcomes and from a public health standpoint to improve surveillance activities.
PMCID: PMC2864639  PMID: 19759489
BSI; mortality; children; Georgia
7.  Prevalence and Risk Factors for Latent Tuberculosis Infection among Health-care Workers in the Country of Georgia 
SUMMARY
BACKGROUND
Tuberculosis (TB) is a major public health problem in Georgia, but few TB infection control measures have been implemented in health-care facilities.
OBJECTIVE
To assess the prevalence and risk factors for latent TB infection (LTBI) among Georgian health-care workers (HCWs) using two diagnostic tests, the tuberculin skin test (TST) and the QuantiFERON-TB in-tube-test (QFT-3G), an interferon-γ release assay.
METHODS
A cross-sectional study was conducted between June-August 2006 among HCWs at the Georgian National TB Program.
RESULTS
265 HCWs were enrolled; 177 (67%) had a positive TST and 159 (60%) had a positive QFT-3G. 203 (77%) had a positive result for at least one of the tests and 50% tested positive for both tests. There was moderately good agreement between the tests (74%, κ=0.43 95% CI 0.33-0.55). In multivariate analysis, employment for >5 years was associated with increased risk of a positive TST (OR=5.09; 95% CI, 2.77-9.33) and QFT-3G (OR=2.26; 95% CI, 1.27-4.01); age >30 years, was associated with an increased risk of a positive QFT-3G (OR=2.91; 95% CI, 1.32-6.43).
DISCUSSION
A high prevalence of LTBI was found among Georgian HCWs and longer duration of employment was associated with increased risk. These data highlight the need for effective TB infection control measures and provide important baseline information as TB infection control measures are implemented.
PMCID: PMC2742226  PMID: 18419886
tuberculosis infection; interferon-γ assay; nosocomial transmission; skin test

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