Survival of Patients with Acquired Immune Deficiency Syndrome and Disseminated<i>Mycobacterium avium</i>Complex Infection with and without Antimycobacterial Chemotherapy

Cr, Horsburgh; Ja, Havlik; Da, Ellis; Kennedy, Eugene P.; Sa, Fann; Re, Dubois; Thompson, Sumner E.

doi:10.1164/ajrccm/144.3_pt_1.557

Cited by 185 publications

(67 citation statements)

References 3 publications

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“…Without antimycobacterial chemotherapy in some form, up to 40% of AIDS patients develop disseminated MAC infection within two years of diagnosis of AIDS (6,12,14,21). Specific serotypes of MAC such as 1, 4, 6, 8, and 16 are isolated frequently from AIDS patients (1,7,10,26,28).…”

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confidence: 99%

Rapid Serodiagnosis of Mycobacterium avium‐intracellulare Complex Infection by ELISA with Cord Factor (Trehalose 6, 6′‐Dimycolate), and Serotyping Using the Glycopeptidolipid Antigen

Enomoto

Oka

Fujiwara

et al. 1998

Microbiology and Immunology

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Mycobacterium avium-intracellulare complex (MAC) is one of the most important opportunistic pathogens, particularly in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to determine whether an enzyme-linked immunosorbent assay (ELISA) using trehalose 6, 6'-dimycolate (TDM) as an antigen can be used for the rapid serodiagnosis of MAC infection. We also identified MAC serotypes by ELISA using serotype-specific glycopeptidolipid (GPL) antigen. To confirm our findings, the thin-layer chromatographic (TLC) behavior of serotype-specific GPL of the strains isolated from MACinfected patients was also tested. Forty patients infected with MAC and 30 healthycontrols were tested. Thirty-two of the 40 MAC-infected patients had higher titers of serum antibodies against MAC TDM than against MTB TDM, while all 30 healthy control sera were unreactive to MAC TDM and MTB TDM. Results of the GPL ELISA indicated that 20 of the 40 MAC-infected patients' sera were reactive against serotype 4 GPL, 3 against serotype 8 GPL, and 1 against serotype 16 GPL. A TLC analysis of the GPL of the 40 MAC isolates showed that 16 strains were of serotype 4, 5 of serotype 8, and 2 of serotype 16. Results of the GPL ELISA were in good accord with those of the TLC analysis for most patients. Our findings suggest that ELISA using TDM is useful for rapid serodiagnosis of MAC infection, and that complementary ELISA testing using serotype-specific GPL gives additional detailed information concerning MAC serotypes.

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confidence: 99%

Rapid Serodiagnosis of Mycobacterium avium‐intracellulare Complex Infection by ELISA with Cord Factor (Trehalose 6, 6′‐Dimycolate), and Serotyping Using the Glycopeptidolipid Antigen

Enomoto

Oka

Fujiwara

et al. 1998

Microbiology and Immunology

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“…The most urgent problem associated with M avium infections in these patients is the lack of definition of a standard optimal antimicrobial therapy. Despite this, however, it is clear that prolonged survival is associated with antimycobacterial treatment, with an average life extension of 8 months (6,18).…”

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confidence: 99%

A bone marrow-derived murine macrophage model for evaluating efficacy of antimycobacterial drugs under relevant physiological conditions

Skinner

Furney

Jacobs

et al. 1994

Antimicrob Agents Chemother

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Even though the macrophage is the host cell for the intracellular bacterial parasite Mycobacterium avium, macrophages have undergone only limited evaluation as models for determining the capacities of antimycobacterial drugs to inhibit the growth of M. avium within this relevant intracellular environment. In the present study, we demonstrated that a panel of M. avium isolates could actively infect homogeneous monolayers of murine bone marrow-derived macrophages. A number of established and experimental antimycobacterial drugs were then added to these cultures at a range of concentrations, and their effects on the numbers of surviving bacilli were determined 8 days later. By plotting such numbers versus drug concentrations it was then possible to clearly distinguish between compounds with bactericidal activity (such as rifabutin and PD 125354) and those with bacteriostatic effects (such as clarithromycin), even though several of these compounds had very similar MICs. In addition, an estimate of the potential therapeutic efficiency of each drug could be made by determining the concentration needed to destroy an arbitrary percentage of the inoculum (in this case, the bactericidal concentration destroying 99%o of the inoculum). Such values were considerably in excess of the MICs and may more realistically reflect the concentrations in serum required to electively reduce the bacterial burden in vivo.

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“…The potential to rapidly identify MAC and other NTM species in countries with a low TB incidence such as the United States is required within many health care systems to rule out MTBC infections and inform critical decisions, including the imposition of quarantine (21). The testing of a limited number of MAC-positive clinical specimens with MID-DRS demonstrated a specificity of 97.8%, indicating that the rapid-detection component for MAC could be a useful tool for high-throughput screening.…”

Section: Discussionmentioning

confidence: 99%

“…Among nontuberculous mycobacteria (NTM), infections by members of the Mycobacterium avium complex (MAC) are among those most frequently diagnosed in countries with a low TB incidence such as the United States (21). Patients with MAC infections can present with clinical manifestations similar to MTBC infections, such as cough, fever, malaise, and weight loss.…”

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confidence: 99%

Rapid Identification of Mycobacteria and Drug-Resistant Mycobacterium tuberculosis by Use of a Single Multiplex PCR and DNA Sequencing

et al. 2012

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Tuberculosis (TB) remains a significant global health problem for which rapid diagnosis is critical to both treatment and control. This report describes a multiplex PCR method, the Mycobacterial IDentification and Drug Resistance Screen (MID-DRS) assay, which allows identification of members of the Mycobacterium tuberculosis complex (MTBC) and the simultaneous amplification of targets for sequencing-based drug resistance screening of rifampin-resistant (rifampin r ), isoniazid r , and pyrazinamide r TB. Additionally, the same multiplex reaction amplifies a specific 16S rRNA gene target for rapid identification of M. avium complex (MAC) and a region of the heat shock protein 65 gene (hsp65) for further DNA sequencing-based confirmation or identification of other mycobacterial species. Comparison of preliminary results generated with MID-DRS versus culturebased methods for a total of 188 bacterial isolates demonstrated MID-DRS sensitivity and specificity as 100% and 96.8% for MTBC identification; 100% and 98.3% for MAC identification; 97.4% and 98.7% for rifampin r TB identification; 60.6% and 100% for isoniazid r TB identification; and 75.0% and 98.1% for pyrazinamide r TB identification. The performance of the MID-DRS was also tested on acid-fast-bacterium (AFB)-positive clinical specimens, resulting in sensitivity and specificity of 100% and 78.6% for detection of MTBC and 100% and 97.8% for detection of MAC. In conclusion, use of the MID-DRS reduces the time necessary for initial identification and drug resistance screening of TB specimens to as little as 2 days. Since all targets needed for completing the assay are included in a single PCR amplification step, assay costs, preparation time, and risks due to user errors are also reduced.T he diagnosis and control of tuberculosis (TB) is a very significant problem in global health. A recent report by the World Health Organization (WHO) estimates that Mycobacterium tuberculosis, the causative agent of the disease, has infected one-third of the world's population (71). TB can persist in a latent state within infected individuals for decades (69). Progression to active disease occurs in approximately 5% to 10% of immunocompetent individuals and triggers the frequent cough that enables the organism to be transmitted (11). Moreover, effective treatment of patients with active TB has become more difficult with the increasing prevalence of multidrug-resistant (MDR) strains (7, 70). MDR-TB is resistant to both of the first-line drugs rifampin (RIF) and isoniazid (INH) (8). MDR-TB cases have been estimated to account for one in four new TB cases in some parts of the world (70). In the United States, MDR-TB cases comprise approximately 1.1% of new TB cases, with the majority of these cases imported from regions where the disease is endemic.All members of the M. tuberculosis complex (MTBC) are capable of causing pulmonary disease, and early diagnosis is the most effective means of TB control. Culture-based identification remains the gold standard method for TB diagnosis (1...

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Survival of Patients with Acquired Immune Deficiency Syndrome and DisseminatedMycobacterium aviumComplex Infection with and without Antimycobacterial Chemotherapy

Cited by 185 publications

References 3 publications

Rapid Serodiagnosis of Mycobacterium avium‐intracellulare Complex Infection by ELISA with Cord Factor (Trehalose 6, 6′‐Dimycolate), and Serotyping Using the Glycopeptidolipid Antigen

Rapid Serodiagnosis of Mycobacterium avium‐intracellulare Complex Infection by ELISA with Cord Factor (Trehalose 6, 6′‐Dimycolate), and Serotyping Using the Glycopeptidolipid Antigen

A bone marrow-derived murine macrophage model for evaluating efficacy of antimycobacterial drugs under relevant physiological conditions

Rapid Identification of Mycobacteria and Drug-Resistant Mycobacterium tuberculosis by Use of a Single Multiplex PCR and DNA Sequencing

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