Mycobacterium Tuberculosis Bacteremia Research Articles

Genesis of Antibiotic Resistance (AR) LVIII: Discordant Antibiotic Stewardship contort Early Goal Directed Fluid Resuscitation therapy (EGDT) with higher incidence of Mortality in severe Sepsis: A global melee

A retrospective analysis of EGDT trials from 2000 to 2018 registered in national clinical trials is presented here: (PRISM‐U) Study group attributed that the sepsis cohort with Mycobacterium tuberculosis (MTB) bacteremia for higher rate of in‐hospital mortality. FEAST (ISRCTN69856593) trial observed that fluid resuscitation in children with sepsis significantly increased mortality (48‐hour) possibly due to impaired perfusion. SSSP trail (NCT01449916) showed that though hypoxemic respiratory failure as contributing factor for mortality in addition to tissue hypoperfusion as inclusion criteria of patients with hypovolemia but excluding the patients with severe respiratory distress when ventilator support is not readily available could have potentially improved the survival rate. ARISE (NCT00975793) presented their report on the effectiveness of EGDT compare to that of usual sepsis care had similar (~18%) mortality rate concluding that EGDT did not reduce all‐cause mortality at 90 days. PRISM (NCT02030158) reported that, EGDT miss the mark to relieve mortality rate compare to that of usual care cohort. ProCESS (NCT00510835) reported that among 1341 patients, of whom 439 were randomly assigned to protocol‐based EGDT, 446 to protocol‐based standard therapy, and 456 to usual care in which protocol‐based resuscitation of patients in whom septic shock was diagnosed in the ER did not improve outcomes. ProMISe (ISRCTN36307479) concluded that septic shock cohort identified early and treated with intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol showed that no difference in mortality rate by 90 days. The IMPreSS study group found that compliance with “all of the evidence‐based bundle metrics” had a 40 % reduction in the odds of dying in hospital with the 3‐h bundle and 36 % for the 6‐h bundle. ProCESS Investigators (NCT00793442, NCT00510835 ) showed that increase in leucocyte rolling and adhering to dysfunctional endothelial surface in the cohort of septic shock compare to that of control, attributed to an increase in endothelial permeability‐hemostasis as cause for mortality. SSSP‐2 (NCT01663701) reported that cohort with sepsis and hypotension, most of whom were positive for HIV, in a resource‐limited setting, a protocol for early resuscitation with administration of intravenous fluids and vasopressors increased in‐hospital mortality compared with usual care. MOSAICS Study Group attributed the high mortality rate in severe sepsis treatment for the variation in adhering to the “all of the evidence‐based bundle metrics” for sepsis treatment. GENESIS project comparing 6‐hour resuscitation bundle (RB) for severe sepsis cohort showed decreased mortality rate compare to that of no RB bundle. Taken together it is suggested that lack coherent antibiotic stewardship practices across the globe warrant immediate review during EGDT and implementation of such guidelines would likely improve the survival rate in both low and high resource setting.Support or Funding InformationSupported by the professional development funds by SWTJC to Subburaj Kannan

Opsonic monoclonal antibodies enhance phagocytic killing activity and clearance of Mycobacterium tuberculosis from blood in a quantitative qPCR mouse model

BackgroundPatients with impaired immunity often have rapid progression of tuberculosis (TB) which can lead to highly lethal Mycobacterium tuberculosis (MTB) sepsis. Opsonic monoclonal antibodies (MABs) directed against MTB that enhance phagocytic killing activity and clearance of MTB from blood may be useful to enhance TB immunity. MethodsBALB/c mice were immunized with ethanol-killed MTB (EK-MTB) and MABs were produced and screened by ELISA for binding to killed and live Mycobacterium smegmatis (SMEG) and MTB. MAB opsonophagocytic killing activity (OPKA) was examined using SMEG with HL60 and U-937 cells and MTB with U-937 cells. Clearance of MTB from blood was evaluated in Institute of Cancer Research (ICR) mice given opsonic anti-MTB MABs or saline (control) 24 h prior to intravenous infusion with 108 CFUs gamma-irradiated MTB (HN878). MTB levels in murine blood collected 0.25, 4 and 24 h post-challenge were assessed by qPCR. MAB binding to peptidoglycan (PGN) was examined by ELISA using PGN cell wall mixture and ultra-pure PGN. ResultsTwo MABs (GG9 and JG7) bound to killed and live SMEG and MTB (susceptible and resistant), and promoted OPKA with live MTB. MAB JG7 significantly enhanced OPKA of MTB. Both MABs significantly enhanced clearance of killed MTB from murine blood at 4 and 24 h as measured by qPCR. These opsonic MABs bound to PGN, a major cell wall constituent. ConclusionsAnti-MTB MABs that promote bactericidal phagocytic activity of MTB and enhance clearance of killed MTB from the blood, may offer an immunotherapeutic approach for treatment of MTB bacteremia or sepsis, and augment treatment of multi-drug resistant (MDR) or extensively drug resistant (XDR) TB.

A Novel, High-sensitivity, Bacteriophage-based Assay Identifies Low-level Mycobacterium tuberculosis Bacteremia in Immunocompetent Patients With Active and Incipient Tuberculosis.

The haematogenous dissemination of Mycobacterium tuberculosis (Mtb) is critical to the pathogenesis of progressive tuberculous infections in animal models. Using a novel, phage-based blood assay, we report the first concordant evidence in well-characterized, immunocompetent human cohorts, demonstrating associations of Mtb bacteremia with progressive phenotypes of latent infection and active pulmonary tuberculosis.

Real-time PCR of whole blood specimens transported in PrimeStore MTM® to detect and monitor MTB bacteremia

Background: Mycobacterium tuberculosis (MTB) is an important cause of bacteremia and sepsis in HIV patients residing in sub-Saharan Africa. Many patients with MTB sepsis go undiagnosed and die within 18 days of presentation, making culture inadequate for detecting MTB in the blood. Objective: To determine the feasibility of ambient temperature transport of blood in PrimeStore MTM® to a distant lab for real-time PCR detection of MTB bacteremia and to monitor clearance of MTB from the blood after therapy. Methods & Materials: BALB/c female mice were injected intravenously with 0.2 mls of ethanol killed MTB (approximately 105 CFU/mL). Two anti-MTB opsonophagocytic bactericidal MABs were used to simulate treatment of MTB sepsis. Mouse monoclonal antibodies (MAB LHN-AB9 or LHN-GG9) or control were given IP using 0.3 mls of sterile PBS 24 hours before MTB challenge. To monitor MTB in the blood, mice were bled at 3 time points: immediately after injection with MTB and again at 4 and 24 hours before MTB challenge. Collected blood was placed into citrate tubes and 0.1ml was transferred into PrimeStore MTM®. Samples were transported at ambient temperature from Gaithersburg, MD to San Antonio, TX. DNA was extracted from blood in PrimeStore MTM® and replicate real-time polymerase chain reactions (PCR) were performed using PrimeMix® MTB Complex on an ABI 7500 Instrument. Results: Blood PCRs on specimens obtained 15 minutes after MTB challenge were positive with an average CT value of 29.8 (range 29.2-30.6). Mice treated with PBS control had MTB detected in the blood by PCR at all time points (at 15 min, 4 and 24 hours post challenge). Mice given anti-TB opsonic MABs cleared the MTB from the blood either by 4 or 24 hours (CT = 40). Conclusion: Blood specimens were efficiently transported to a central lab to detect MTB bacteremia by PCR. In addition, PCR may be useful to monitor patient treatment, similar to viral load testing for HIV. Using PrimeStore MTM® to ship specimens safely and rapidly at ambient temperature to a regional facility for PCR analysis may provide rural hospitals in sub-Saharan Africa the opportunity to diagnose MTB sepsis and monitor treatment.

High prevalence of Mycobacterium tuberculosis bacteraemia among a cohort of HIV-infected patients with severe sepsis in Lusaka, Zambia.

Tuberculosis is recognised as one of the leading causes of severe sepsis among HIV-infected patients. Most patients with Mycobacterium tuberculosis bacteraemia have advanced HIV disease with CD4 counts less than 100 cells/μl and its presentation is non-specific in most instances. This was a cross-sectional study which was done by analyzing data from 201 adult HIV-infected patients who met the inclusion criteria for severe sepsis. The prevalence of Mycobacterium tuberculosis bactraemia in the study population was 34.8%. Severe sepsis caused by other etiologies was observed in 33 (16.4%) of the participants. Concomitant infection of Mycobacterium tuberculosis bactraemia with other organisms is not uncommon in patients with severe sepsis. This cohort of HIV-infected patients had severe immunosuppression with a median CD4 count of 51 (20-136) cells/μl with moderate anaemia, mean haemoglobin 8.0 (3.0) g/dl, and were generally underweight with a mean mid upper arm circumference (MUAC) of 21.0 (3.4) cm. Mycobacterium tuberculosis bacteraemia is very common in HIV-infected patients with advanced HIV disease who present with severe sepsis. Mycobacterium tuberculosis bacteraemia co-infection with aerobic organisms is not uncommon. Factors that were independently associated with Mycobacterium tuberculosis bacteraemia in our study population were MUAC and sodium level.

Mycobacterium tuberculosis Bacteremia Among Acutely Febrile Children in Western Kenya.

In children, Mycobacterium tuberculosis (M. tuberculosis) frequently disseminates systemically, presenting with nonspecific signs including fever. We determined prevalence of M. tuberculosis bacteremia among febrile children presenting to hospitals in Nyanza, Kenya (a region with high human immunodeficiency virus (HIV) and M. tuberculosis prevalence). Between March 2013 and February 2014, we enrolled children aged 6 months to 5 years presenting with fever (axillary temperature ≥ 37.5°C) and no recent antibiotic use. Blood samples were collected for bacterial and mycobacterial culture using standard methods. Among 148 children enrolled, median age was 3.1 years (interquartile range: 1.8-4.1 years); 10.3% of children were living with a household member diagnosed with M. tuberculosis in the last year. Seventeen percent of children were stunted (height-for-age z-score < -2), 18.6% wasted (weight-for-height z-score < -2), 2.7% were HIV-infected, and 14.2% were HIV-exposed uninfected. Seventeen children (11.5%) had one or more signs of tuberculosis (TB). All children had a Bacille Calmette-Guerin vaccination scar. Among 134 viable blood cultures, none (95% confidence interval: 0-2.7%) had Mycobacterium isolated. Despite exposure to household TB contacts, HIV exposure, and malnutrition, M. tuberculosis bacteremia was not detected in this pediatric febrile cohort, a finding consistent with other pediatric studies.

Predictors and outcomes of Mycobacterium tuberculosis bacteremia among patients with HIV and tuberculosis co-infection enrolled in the ACTG A5221 STRIDE study.

BackgroundWe evaluated predictors and outcomes of Mycobacterium tuberculosis bacteremia among participants undergoing baseline mycobacterial blood culture in the ACTG A5221 STRIDE study, a randomized clinical trial comparing earlier with later ART among HIV-infected patients suspected of having tuberculosis with CD4-positive T-lymphocyte counts (CD4 counts) <250 cells/mm3. We conducted a secondary analysis comparing participants with respect to presence or absence of M. tuberculosis bacteremia.MethodsParticipants with a baseline mycobacterial blood culture were compared with respect to the presence or absence of M. tuberculosis bacteremia. Baseline predictors of M. tuberculosis bacteremia were identified and participant outcomes were compared by mycobacteremia status.ResultsOf 90 participants with baseline mycobacterial blood cultures, 29 (32.2%) were female, the median (IQR) age was 37 (31–45) years, CD4 count was 81 (33–131) cells/mm3, HIV-1 RNA level was 5.39 (4.96–5.83) log10 copies/mL, and 18 (20.0%) had blood cultures positive for M. tuberculosis. In multivariable analysis, lower CD4 count (OR 0.85 per 10-cell increase, p = 0.012), hemoglobin ≤8.5 g/dL (OR 5.8, p = 0.049), and confirmed tuberculosis (OR 17.4, p = 0.001) were associated with M. tuberculosis bacteremia. There were no significant differences in survival and AIDS-free survival, occurrence of tuberculosis immune reconstitution inflammatory syndrome (IRIS), or treatment interruption or discontinuation by M. tuberculosis bacteremia status. IRIS did not differ significantly between groups despite trends toward more virologic suppression and greater CD4 count increases at week 48 in the bacteremic group.ConclusionsAmong HIV-infected tuberculosis suspects, lower CD4 count, hemoglobin ≤8.5 g/dL, and the presence of microbiologically confirmed pulmonary tuberculosis were associated with increased adjusted odds of mycobacteremia. No evidence of an association between M. tuberculosis bacteremia and the increased risk of IRIS was detected.Trial registrationClinicalTrials.gov: NCT00108862.

Mycobacterium tuberculosis bacteraemia: experience from a non-endemic urban centre.

The isolation of Mycobacterium tuberculosis from blood culture specimens has been associated with human immunodeficiency virus (HIV) co-infection with variable impact on tuberculosis (TB) mortality reported. The overwhelming majority of M. tuberculosis bacteraemia cases were described in developing countries. We present a nested case-control analysis of clinical, sociodemographic and behavioural risk factors in patients with positive M. tuberculosis blood cultures compared with patients with negative blood cultures from a 9-year population-based active TB surveillance study conducted in Houston, Texas. There were 42 patients with M. tuberculosis bacteraemia, 47 blood culture negative patients and 3573 patients for whom no mycobacterial blood culture was requested. HIV infection was more common in patients for whom a mycobacterial blood culture was requested (79.8% versus 15.1% p <0.001). Of the patients with M. tuberculosis bacteraemia, six were HIV negative or had no documentation of HIV status, including five with immunosuppressive conditions other than HIV. Patients with M. tuberculosis bacteraemia were more likely than patients with negative blood cultures to be deceased at diagnosis or to die while on TB therapy (50.0% versus 17.0%, p <0.01), to report men-who-have-sex-with-men behaviour (31.7% versus 13.0%, p 0.03), to have renal failure (28.6% versus 6.4%, p 0.01), and to have HIV RNA levels higher than 500 000 copies/mL (61.9% versus 17.2%, p ≤0.01). Requests for mycobacterial culture of blood specimens were more common in HIV-infected individuals, and the presence of M. tuberculosis bacteraemia was associated with a significant increase in mortality.

Correction: Mycobacterium tuberculosis Bacteremia in a Cohort of HIV-Infected Patients Hospitalized with Severe Sepsis in Uganda–High Frequency, Low Clinical Sand Derivation of a Clinical Prediction Score

Correction: Mycobacterium tuberculosis Bacteremia in a Cohort of HIV-Infected Patients Hospitalized with Severe Sepsis in Uganda–High Frequency, Low Clinical Sand Derivation of a Clinical Prediction Score

Mycobacterium tuberculosis Bacteremia in a Cohort of HIV-Infected Patients Hospitalized with Severe Sepsis in Uganda–High Frequency, Low Clinical Sand Derivation of a Clinical Prediction Score

BackgroundWhen manifested as Mycobacterium tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti-tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia.MethodsWe prospectively enrolled adult patients with severe sepsis at two Ugandan hospitals and obtained blood cultures for MTB identification. Multivariable logistic regression modeling was used to determine predictors of MTB bacteremia and to inform the stratification of patients into MTB bacteremia risk categories based on relevant patient characteristics.ResultsAmong 368 HIV-infected patients with a syndrome of severe sepsis, eighty-six (23%) had MTB bacteremia. Patients with MTB bacteremia had a significantly lower median CD4 count (17 vs 64 lymphocytes/mm3, p<0.001) and a higher 30-day mortality (53% vs 32%, p = 0.001) than patients without MTB bacteremia. A minority of patients with MTB bacteremia underwent standard MTB diagnostic testing (24%) or received empiric anti-tuberculosis therapy (15%). Independent factors associated with MTB bacteremia included male sex, increased heart rate, low CD4 count, absence of highly active anti-retroviral therapy, chief complaint of fever, low serum sodium and low hemoglobin. A risk score derived from a model containing these independent predictors had good predictive accuracy [area under the curve = 0.85, 95% CI 0.80–0.89].ConclusionsNearly 1 in 4 adult HIV-infected patients hospitalized with severe sepsis in 2 Ugandan hospitals had MTB bacteremia. Among patients in whom MTB was suspected, standard tests for diagnosing pulmonary MTB were inaccurate for correctly classifying patients with or without bloodstream MTB infection. A MTB bacteremia risk score can improve early diagnosis of MTB bacteremia particularly in settings with increased HIV and MTB co-infection.

Evaluation of Xpert MTB/RIF for Detection of Tuberculosis from Blood Samples of HIV-Infected Adults Confirms Mycobacterium tuberculosis Bacteremia as an Indicator of Poor Prognosis

Tuberculosis (TB) remains a leading cause of death among HIV-infected adults, in part because of delayed diagnosis and therefore delayed initiation of treatment. Recently, the Gene-Xpert platform, a rapid, PCR-based diagnostic platform, has been validated for the diagnosis of TB with sputum. We have evaluated the Xpert MTB/RIF assay for the diagnosis of Mycobacterium tuberculosis bacteremia and investigated its impact on clinical outcomes. Consecutive HIV-infected adults with fever and cough presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, were recruited and followed up for 2 months. At presentation, three sputum samples were examined by smear, culture, and Xpert MTB/RIF assay for the presence of M. tuberculosis and blood was drawn for PCR with Xpert, for mycobacterial culture (Myco/F Lytic), and for aerobic culture. One hundred four patients were recruited, and 44 (43%) were sputum culture positive for M. tuberculosis. Ten were Xpert blood positive, for a sensitivity of 21% and a specificity of 100%. The 2-week mortality rate was significantly higher among patients who were Xpert blood positive than among those who were negative (40% versus 3%; multivariate odds ratio [OR] for death if positive, 44; 95% confidence interval [CI], 3 to 662). This effect persisted on assessment of the mortality rate at 2 months (40% versus 11%; OR, 5.6; 95% CI, 1.3 to 24.6). When screening uncomplicated patients presenting with a productive cough for pulmonary TB, Xpert blood offers no diagnostic advantage over sputum testing. Despite this, Xpert blood positivity is highly predictive of early death and this test rapidly identifies a group of patients in urgent need of initiation of treatment.

Bacteremic Disseminated Tuberculosis in Sub-Saharan Africa: A Prospective Cohort Study

Disseminated tuberculosis is a major health problem in countries where generalized human immunodeficiency virus (HIV) infection epidemics coincide with high tuberculosis incidence rates; data are limited on patient outcomes beyond the inpatient period. We enrolled consecutive eligible febrile inpatients in Moshi, Tanzania, from 10 March 2006 through 28 August 2010; those with Mycobacterium tuberculosis bacteremia were followed up monthly for 12 months. Survival, predictors of bacteremic disseminated tuberculosis, and predictors of death were assessed. Antiretroviral therapy (ART) and tuberculosis treatment were provided. A total of 508 participants were enrolled; 29 (5.7%) had M. tuberculosis isolated by blood culture. The median age of all study participants was 37.4 years (range, 13.6-104.8 years). Cough lasting >1 month (odds ratio [OR], 13.5; P< .001), fever lasting >1 month (OR, 7.8; P = .001), weight loss of >10% (OR, 10.0; P = .001), lymphadenopathy (OR 6.8; P = .002), HIV infection (OR, undefined; P < .001), and lower CD4 cell count and total lymphocyte count were associated with bacteremic disseminated tuberculosis. Fifty percent of participants with M. tuberculosis bacteremia died within 36 days of enrollment. Lower CD4 cell count (OR, 0.88; P = .049) and lower total lymphocyte count (OR, 0.76; P = .050) were associated with death. Magnitude of mycobacteremia tended to be higher among those with lower CD4 cell counts, but did not predict death. In the era of free ART and access to tuberculosis treatment, almost one half of patients with M. tuberculosis bacteremia may die within a month of hospitalization. Simple clinical assessments can help to identify those with the condition. Advanced immunosuppression predicts death. Efforts should focus on early diagnosis and treatment of HIV infection, tuberculosis, and disseminated disease.

Performance of Nucleic Acid Amplification following Extraction of 5 Milliliters of Whole Blood for Diagnosis of Mycobacterium tuberculosis Bacteremia

To investigate the performance of a nucleic acid amplification test (NAAT) for the diagnosis of Mycobacterium tuberculosis bacteremia, 5-ml aliquots of blood were inoculated into bioMérieux mycobacterial (MB) bottles and incubated, and 5-ml aliquots of blood were extracted and tested by real-time PCR. Of 25 samples from patients with M. tuberculosis bacteremia, 9 (36.0%) were positive and 1 (1.5%) of 66 control samples was positive by NAAT. The NAAT shows promise, but modifications should focus on improving sensitivity.

Controlled Comparison of BacT/Alert MB System, Manual Myco/F Lytic Procedure, and Isolator 10 System for Diagnosis of Mycobacterium tuberculosis Bacteremia

We compared the performance of the BacT/Alert MB system, that of the manual Bactec Myco/F Lytic procedure, and that of the Isolator 10 lysis-centrifugation system in the detection of Mycobacterium tuberculosis bacteremia. Mean times to detection were 16.4 days for BacT/Alert MB versus 20.0 days for Myco/F Lytic, 16.5 days for BacT/Alert MB versus 23.8 days for Isolator 10, and 21.1 days for Bactec Myco/F Lytic versus 22.7 days for Isolator 10. There were no significant differences in yields. The mean (range) magnitude of mycobacteremia was 30.0 (0.4, 90.0) CFU/ml and was correlated with the time to positivity in the BacT/Alert MB system (r = -0.4920). M. tuberculosis bacteremia was detected more rapidly in a continuously monitored liquid blood culture system, but the mean time to positivity exceeded 3 weeks.

Blood cultures for the diagnosis of multidrug-resistant and extensively drug-resistant tuberculosis among HIV-infected patients from rural South Africa: a cross-sectional study

BackgroundThe yield of mycobacterial blood cultures for multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) among drug-resistant TB suspects has not been described.MethodsWe performed a retrospective, cross-sectional analysis to determine the yield of mycobacterial blood cultures for MDR-TB and XDR-TB among patients suspected of drug-resistant TB from rural South Africa. Secondary outcomes included risk factors of Mycobacterium tuberculosis bacteremia and the additive yield of mycobacterial blood cultures compared to sputum culture.ResultsFrom 9/1/2006 to 12/31/2008, 130 patients suspected of drug-resistant TB were evaluated with mycobacterial blood culture. Each patient had a single mycobacterial blood culture with 41 (32%) positive for M. tuberculosis, of which 20 (49%) were XDR-TB and 8 (20%) were MDR-TB. One hundred fourteen (88%) patients were known to be HIV-infected. Patients on antiretroviral therapy were significantly less likely to have a positive blood culture for M. tuberculosis (p = 0.002). The diagnosis of MDR or XDR-TB was made by blood culture alone in 12 patients.ConclusionsMycobacterial blood cultures provided an additive yield for diagnosis of drug-resistant TB in patients with HIV from rural South Africa. The use of mycobacterial blood cultures should be considered in all patients suspected of drug-resistant TB in similar settings.

Mycobacterial bacteraemia in patients infected and not infected with human immunodeficiency virus, Taiwan

The clinical characteristics and outcomes of 71 patients with mycobacterial bacteraemia, infected with human immunodeficiency virus (HIV) (n = 47) and not infected with HIV (n = 24) are described. Mycobacterium avium complex (MAC) (54.9%) constituted the most frequently isolated mycobacterium, followed by Mycobacterium tuberculosis (MTB) (38.0%), Mycobacterium kansasii (4.2%), and Mycobacterium abscessus (2.8%). The Beijing family genotype was the most common type in MTB, and Mycobacterium intracellulare was the most common species in MAC. The overall mortality rate was 33.8%; it was lower in HIV-infected than in non-HIV-infected patients. HIV-infected patients were younger, had fewer underlying diseases and better nutritional status, and were more likely to have MAC bacteraemia than MTB bacteraemia.

Severe Sepsis in Two Ugandan Hospitals: a Prospective Observational Study of Management and Outcomes in a Predominantly HIV-1 Infected Population

BackgroundSepsis likely contributes to the high burden of infectious disease morbidity and mortality in low income countries. Data regarding sepsis management in sub-Saharan Africa are limited. We conducted a prospective observational study reporting the management and outcomes of severely septic patients in two Ugandan hospitals. We describe their epidemiology, management, and clinical correlates for mortality.Methodology/ResultsThree-hundred eighty-two patients fulfilled enrollment criteria for a severe sepsis syndrome. Vital signs, management and laboratory results were recorded. Outcomes measured included in-hospital and post-discharge mortality.Most patients were HIV-infected (320/377, 84.9%) with a median CD4+ T cell (CD4) count of 52 cells/mm3 (IQR, 16–131 cells/mm3). Overall mortality was 43.0%, with 23.7% in-hospital mortality (90/380) and 22.3% post-discharge mortality (55/247). Significant predictors of in-hospital mortality included admission Glasgow Coma Scale and Karnofsky Performance Scale (KPS), tachypnea, leukocytosis and thrombocytopenia. Discharge KPS and early fluid resuscitation were significant predictors of post-discharge mortality. Among HIV-infected patients, CD4 count was a significant predictor of post-discharge mortality.Median volume of fluid resuscitation within the first 6 hours of presentation was 500 mLs (IQR 250–1000 mls). Fifty-two different empiric antibacterial regimens were used during the study. Bacteremic patients were more likely to die in hospital than non-bacteremic patients (OR 1.83, 95% CI = 1.01–3.33). Patients with Mycobacterium tuberculosis (MTB) bacteremia (25/249) had higher in-hospital mortality (OR 1.97, 95% CI = 1.19–327) and lower median CD4 counts (p = 0.001) than patients without MTB bacteremia.ConclusionPatients presenting with sepsis syndromes to two Ugandan hospitals had late stage HIV infection and high mortality. Bacteremia, especially from MTB, was associated with increased in-hospital mortality. Most clinical predictors of in-hospital mortality were easily measurable and can be used for triaging patients in resource-constrained settings. Procurement of low cost and high impact treatments like intravenous fluids and empiric antibiotics may help decrease sepsis-associated mortality in resource-constrained settings.

Fever of unknown origin in patients with HIV infection in Thailand: an observational study and review of the literature

Fever of unknown origin (FUO) is a common presentation for patients with advanced human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). We prospectively followed 72 patients, consecutively admitted to a Thai regional hospital with FUO and HIV infection to identify aetiologies and mortality in the era of available antiretroviral therapy (ART). Aetiologies of FUO were identified in 67 patients (93%), of whom 61(85%) had an infectious aetiology. The most common infectious aetiologies were Mycobacterium tuberculosis (n=30; 42%), Cryptococcus neoformans (n=17; 24%), Pneumocystis jiroveci (n=9; 13%), Toxoplasma gondii (n=5; 7%), and salmonella bacteraemia (n=5; 7%). Nineteen patients (26%) had co-infection with two or more pathogens. The median CD4 count was 120 cells/mm(3) (range, 1-581 cells/mm(3)), and the all-cause mortality was 22% (n=16). By multivariate analysis, inadequate antimicrobial treatment was the sole predictor of mortality (aOR=4.9; 95% CI=1.2-21.9; P=0.02). Overall, 58 of 72 patients (81%) had an opportunistic infection suggesting that guideline use of ART and prophylactic strategies remain unmet needs that will benefit individuals and populations with HIV/AIDS in Thailand.

Mycobacterium tuberculosis Bacteremia in HIV-negative Patients

Limited information exists about the epidemiologic characteristics of HIV-negative patients with Mycobacterium tuberculosis bacteremia (MTB). We retrospectively surveyed tuberculosis (TB) cases reported at National Taiwan University Hospital between 1997 and 2003. Demographic data, underlying diseases or conditions, clinical, microbiologic and radiologic findings and therapy were collected. Long-term outcome was evaluated at 1 year after initiation of anti-TB agents. During the study period the incidence of MTB bacteremia in HIV-negative patients and HIV-positive patients were 0.024 and 6.2 per 1000 discharges, respectively (p<0.01). All 11 HIV-negative patients were males and eight (73%) were more than 50 years old. The most common underlying diseases/conditions were immunosuppressive therapy (64%) and heart disease (55%). Fever (80%), lymphopenia (75%) and pulmonary symptoms (58%) were the most common presentations. Ten patients were septic, two had septic shock and two had acute respiratory distress syndrome on admission. The median interval between admission and initiation of therapy for those who were cured was 6 days. Six (55%) died of TB and/or their underlying diseases. Of the six patients who died, the median survival after collection of positive blood culture was 19 days for three treated patients and 7 days for three untreated patients (p=0.01). This case series demonstrates the wide spectrum of the initial presentation of HIV-negative patients with MTB bacteremia. The case fatality rate was high and was likely due to immunocompromised status and no anti-TB treatment prior to death. A high index of suspicion for TB and blood culture for MTB provides an additional simple and noninvasive diagnostic method to detect disseminated TB in endemic areas.

Unrecognised Mycobacterium tuberculosis bacteraemia among hospital inpatients in less developed countries

Nosocomial transmission of Mycobacterium tuberculosis is a global public-health concern. Although early clinical recognition of M. tuberculosis in hospital inpatients is critical for effective infection control, such recognition may be difficult in patients with HIV infection. To find out whether M. tuberculosis bacteraemia frequently goes unrecognised, we did a prospective blood-culture survey in an infectious-diseases hospital in Thailand and a general hospital in Malawi. Consecutive febrile (> or = 37.5 degrees C axillary or > or = 38.0 degrees C orally) hospital inpatients (aged > or = 18 years) were enrolled; blood was obtained for mycobacterial culture and HIV testing. Simple diagnostic tests, such as chest radiographs and sputum smears, were ordered by clinicians as deemed necessary, and were carried out with existing local resources. Of 344 patients enrolled, 255 (74%) were HIV infected, the median age was 33 years (range 18-87), and 208 (61%) were male. 34 (10%) patients had M. tuberculosis bacteraemia; five of these patients were already on antituberculosis therapy. Only HIV-infected patients had M. tuberculosis bacteraemia. Of the 29 patients with M. tuberculosis bacteraemia who were not already receiving antituberculosis therapy, 13 (45%) had an abnormal chest radiograph or a positive sputum smear. 16 (55%) patients had no additional diagnostic test results to indicate M. tuberculosis infection; 18 (81%) of these had a cough. In less developed countries where both M. tuberculosis and HIV infections are prevalent, M. tuberculosis bacteraemia may frequently go unrecognised among febrile hospital inpatients.