Controversies in the Management of Mycobacterium Avium Complex Infection in AIDS Patients

1993 ◽  
Vol 27 (7-8) ◽  
pp. 928-937 ◽  
Author(s):  
Charles A. Peloquin
Keyword(s):  
Mouse Models ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Susceptibility Testing ◽  
Traditional Approach ◽  
Clinical Manifestations ◽  
Future Research ◽  
General Description ◽  
Aids Patients

OBJECTIVE: To update readers on the clinical management of infections secondary to Mycobacterium avium complex (MAC) in patients with AIDS. A general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease is provided. Several aspects of the treatment of the disease, including an historical perspective, current approaches, and future research opportunities, are described. DATA SOURCES: Current medical literature, including abstracts presented at international meetings, is reviewed. References were identified through MEDLINE, Current Contents, and published meeting abstracts. STUDY SELECTION: Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of MAC are cited. Specific attention is given to the management of patients with MAC infection. DATA EXTRACTION: Information contributing to the discussion of the topics selected by the author is reviewed. Data supporting and disputing specific conclusions are presented. DATA SYNTHESIS: Disseminated MAC infection is diagnosed antemortem in approximately 30 percent of patients with AIDS; postmortem rates of isolation exceed 50 percent. The incidence of MAC may increase as attempts at isolating the organism become more aggressive. The traditional approach to the isolation, susceptibility testing, and treatment of MAC has been derived from the management of Mycobacterium tuberculosis, with disappointing results. Newer radiometric in vitro methods of susceptibility testing appear to show more promise. Current mouse models of MAC are not true AIDS models; new CD4-deficient mouse models are being developed. Clinical mycobacteriologic and pharmacokinetic laboratory support have been underused, with treatment generally proceeding empirically. New agents that may contribute to the management of disseminated MAC infection include the macrolide derivatives clarithromycin and azithromycin. Research also continues with new rifamycins (including rifabutin) and fluoroquinolones (ciprofloxacin, sparfloxacin). Preliminary results suggest a central role for macrolides in the treatment of disseminated MAC; effective companion drugs are needed to prevent the rapid emergence of macrolide-resistant MAC. CONCLUSIONS: Treatment results for disseminated MAC infection remain poor. Therapy may be improved by selecting drugs on the basis of susceptibility data for each isolate, rather than by using empiric regimens based on susceptibility trends. Significant antimycobacterial drug malabsorption has been documented, and may contribute to poor outcomes. More-potent agents are needed to improve the clinical outcome in AIDS patients with MAC.

Rifabutin: A Review with Emphasis on its Role in the Prevention of Disseminated Mycobacterium Avium Complex Infection

1994 ◽  
Vol 28 (11) ◽  
pp. 1250-1254 ◽  
Author(s):  
Daniel S. Maddix ◽  
Kimberly B. Tallian ◽  
Paul S. Mead
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Aids Patients ◽  
Double Blind ◽  
Medline Search ◽  
Cd4 Lymphocyte

OBJECTIVE: To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of rifabutin. DATA SOURCES: Pertinent literature published between 1982 and 1993 was identified via a MEDLINE search. Published proceedings of selected conferences were also reviewed. STUDY SELECTION: Selected basic science, microbiologic, and pharmacokinetic articles were evaluated. Because only limited data regarding rifabutin were available in the literature, all clinical trials involving the use of rifabutin in the prevention of Mycobacterium avium complex (MAC) infection in AIDS patients were reviewed. DATA SYNTHESIS: Rifabutin is a rifamycin derivative that was approved recently for the prevention of disseminated MAC disease in patients with advanced HIV infection. The drug has in vitro and in vivo activity against gram-positive bacteria, gram-negative bacteria, and mycobacteria. Two prospective, randomized, double-blind, placebo-controlled, multicenter trials demonstrated that rifabutin decreased the progression to MAC bacteremia in AIDS patients by about 50 percent. Adverse effects that resulted in the discontinuation of rifabutin prophylaxis occurred in 16 percent of patients. Rifabutin induces hepatic enzymes to a lesser extent than does rifampin, but dosage adjustment of drugs that are known to interact with rifampin may be required. CONCLUSIONS: Rifabutin is the only drug shown to be effective in the prevention of MAC bacteremia in AIDS patients; therefore, it should be made available as a formulary agent. It may be reasonable to delay initiation of rifabutin prophylaxis until CD4 lymphocyte counts are less than 75–50/mm3.

scholarly journals In Vitro Susceptibility Testing of Bedaquiline against Mycobacterium avium Complex

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Barbara A. Brown-Elliott ◽  
Julie V. Philley ◽  
David E. Griffith ◽  
Foram Thakkar ◽  
Richard J. Wallace
Keyword(s):  
Cytochrome P450 ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Content Type ◽  
In Vitro Susceptibility Testing

ABSTRACT We performed bedaquiline broth microdilution susceptibility testing using Clinical and Laboratory Standards Institute (CLSI) guidelines on 103 respiratory isolates of Mycobacterium avium complex (MAC), including multidrug-resistant isolates. Approximately 90% of isolates had bedaquiline MICs of ≤0.008 μg/ml, and 102/103 isolates had MICs of ≤0.015 μg/ml. Bedaquiline has excellent potential for use in patients with MAC infections, although for reasons of its metabolism by the cytochrome P450 system, it should not be given with rifampin.

scholarly journals Multisite Reproducibility of Results Obtained by Two Broth Dilution Methods for Susceptibility Testing of Mycobacterium avium Complex

2003 ◽  
Vol 41 (2) ◽  
pp. 627-631 ◽  
Author(s):  
G. L. Woods ◽  
N. Williams-Bouyer ◽  
R. J. Wallace ◽  
B. A. Brown-Elliott ◽  
F. G. Witebsky ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Reproducibility Of Results ◽  
Mycobacterium Avium Complex ◽  
Susceptibility Testing ◽  
Broth Dilution

scholarly journals γδ T cells increase with Mycobacterium avium complex infection but not with tuberculosis in AIDS patients

1999 ◽  
Vol 11 (9) ◽  
pp. 1475-1478 ◽  
Author(s):  
J.-L. Pellegrin ◽  
J.-L. Taupin ◽  
M. Dupon ◽  
J.-M. Ragnaud ◽  
J. Maugein ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Γδ T Cells ◽  
Aids Patients ◽  
Mycobacterium Avium Complex Infection

scholarly journals Effective Treatment of Mycobacterium avium subsp. hominissuis and Mycobacterium abscessus Species Infections in Macrophages, Biofilm, and Mice by Using Liposomal Ciprofloxacin

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
James D. Blanchard ◽  
Valerie Elias ◽  
David Cipolla ◽  
Igor Gonda ◽  
Luiz E. Bermudez
Keyword(s):  
Effective Treatment ◽  
Mouse Models ◽  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Mycobacterium Abscessus ◽  
Content Type ◽  
Number Of Individuals ◽  
Intranasal Instillation

ABSTRACT Nontuberculous mycobacteria (NTM) affect an increasing number of individuals worldwide. Infection with these organisms is more common in patients with chronic lung conditions, and treatment is challenging. Quinolones, such as ciprofloxacin, have been used to treat patients, but the results have not been encouraging. In this report, we evaluate novel formulations of liposome-encapsulated ciprofloxacin (liposomal ciprofloxacin) in vitro and in vivo. Its efficacy against Mycobacterium avium and Mycobacterium abscessus was examined in macrophages, in biofilms, and in vivo using intranasal instillation mouse models. Liposomal ciprofloxacin was significantly more active than free ciprofloxacin against both pathogens in macrophages and biofilms. When evaluated in vivo, treatment with the liposomal ciprofloxacin formulations was associated with significant decreases in the bacterial loads in the lungs of animals infected with M. avium and M. abscessus. In summary, topical delivery of liposomal ciprofloxacin in the lung at concentrations greater than those achieved in the serum can be effective in the treatment of NTM, and further evaluation is warranted.

scholarly journals Models of multiple system atrophy

2019 ◽  
Vol 51 (11) ◽  
pp. 1-10 ◽  
Author(s):  
He-Jin Lee ◽  
Diadem Ricarte ◽  
Darlene Ortiz ◽  
Seung-Jae Lee
Keyword(s):  
Animal Models ◽  
Multiple System Atrophy ◽  
Mouse Models ◽  
Clinical Manifestations ◽  
Lewy Bodies ◽  
Model Systems ◽  
Future Research ◽  
Cytoplasmic Inclusions ◽  
Cellular Models ◽  
Brain Extracts

AbstractMultiple system atrophy (MSA) is a neurodegenerative disease with diverse clinical manifestations, including parkinsonism, cerebellar syndrome, and autonomic failure. Pathologically, MSA is characterized by glial cytoplasmic inclusions in oligodendrocytes, which contain fibrillary forms of α-synuclein. MSA is categorized as one of the α-synucleinopathy, and α-synuclein aggregation is thought to be the culprit of the disease pathogenesis. Studies on MSA pathogenesis are scarce relative to studies on the pathogenesis of other synucleinopathies, such as Parkinson’s disease and dementia with Lewy bodies. However, recent developments in cellular and animal models of MSA, especially α-synuclein transgenic models, have driven advancements in research on this disease. Here, we review the currently available models of MSA, which include toxicant-induced animal models, α-synuclein-overexpressing cellular models, and mouse models that express α-synuclein specifically in oligodendrocytes through cell type-specific promoters. We will also discuss the results of studies in recently developed transmission mouse models, into which MSA brain extracts were intracerebrally injected. By reviewing the findings obtained from these model systems, we will discuss what we have learned about the disease and describe the strengths and limitations of the models, thereby ultimately providing direction for the design of better models and future research.

Nocardia spp.: A Rare Cause of Pneumonia Globally

2020 ◽  
Vol 41 (04) ◽  
pp. 538-554
Author(s):  
Joseph P. Lynch ◽  
Gail Reid ◽  
Nina M. Clark
Keyword(s):  
Susceptibility Testing ◽  
Organ Transplant ◽  
Clinical Manifestations ◽  
Community Acquired Pneumonia ◽  
Solid Organ ◽  
In Vitro Susceptibility ◽  
Timely Initiation ◽  
Life Threatening ◽  
Initiation Of Therapy

AbstractMembers of the Nocardia genus are ubiquitous in the environment. These aerobic, gram-positive organisms can lead to life-threatening infection, typically in immunocompromised hosts such as solid organ transplant recipients or those receiving immunosuppressive medications for other reasons. This current review discusses the microbiology of nocardiosis, risk factors for infection, clinical manifestations, methods for diagnosis, and treatment. Nocardiosis primarily affects the lung but may also cause skin and soft tissue infection, cerebral abscess, bloodstream infection, or infection involving other organs. Although rare as a cause of community-acquired pneumonia, Nocardia can have severe morbidity and mortality, particularly in patients with comorbidities or compromised immunity. Early diagnosis and timely initiation of therapy are critical to optimizing patient outcomes. Species identification is important in determining treatment, as is in vitro susceptibility testing. Sulfonamide therapy is usually indicated, although a variety of other antimicrobials may be useful, depending on the species and susceptibility testing. Prolonged therapy is usually indicated, for 6 to 12 months, and in some cases surgical debridement may be required to resolve infection.

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