RESUMO
BACKGROUND: Nontuberculous mycobacteria are environmental organisms that cause infections leading to chronic, debilitating pulmonary disease, among which Mycobacterium avium complex (MAC) is the most common species. METHODS: We described patterns of macrolide-based multidrug antibiotic therapies for MAC pulmonary disease (MAC-PD) in US Medicare beneficiaries with bronchiectasis between January 2006 and December 2014. MAC therapy was defined as a multidrug regimen containing a macrolide plus ≥1 other drug targeting MAC-PD (rifamycin, ethambutol, fluoroquinolone, or amikacin) prescribed concomitantly for >28 days. RESULTS: We identified 9189 new MAC therapy users, with a mean age (standard deviation) of 74 (6 years) at the start of therapy; 75% female and 87% non-Hispanic white. A guideline-based regimen (a macrolide, ethambutol, and rifamycin, with or without amikacin) was prescribed for 51% of new MAC therapy users at treatment start, of whom 41% were continuing guideline-based therapy at 6 months, and only 18% at 12 months. Of all new MAC therapy users, by 18 months only 11% were still receiving MAC treatment, 55% had discontinued therapy, and 34% were censored owing to death or the end of the study period. CONCLUSIONS: Overall, nearly half of new MAC therapy users were prescribed a non-guideline-recommended macrolide-based therapy, including regimens commonly associated with promoting macrolide resistance. Treatment discontinuation was common, and once discontinued, only a few beneficiaries resumed therapy at a later time. Our study adds important data to the current literature on treatment patterns for MAC-PD among older US populations. Future research should examine treatment patterns using more contemporary data sources.
Assuntos
Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Rifamicinas , Idoso , Humanos , Feminino , Estados Unidos , Masculino , Complexo Mycobacterium avium , Antibacterianos/uso terapêutico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Etambutol/uso terapêutico , Amicacina/uso terapêutico , Macrolídeos/uso terapêutico , Farmacorresistência Bacteriana , Medicare , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Rifamicinas/uso terapêutico , Quimioterapia CombinadaRESUMO
BACKGROUND: Recently, Mycobacterium avium complex (MAC) infections have been increasing, especially in immunocompromised and older adults. The rapid increase has triggered a global health concern due to limited therapeutic strategies and adverse effects caused by long-term medication. To provide more evidence for the treatment of MAC, we studied the in vitro inhibitory activities of 17 antimicrobial agents against clinical MAC isolates. RESULTS: A total of 111 clinical MAC isolates were enrolled in the study and they were identified as M. intracellulare, M. avium, M. marseillense, M. colombiense, M. yongonense, and two isolates could not be identified at the species level. MAC strains had relatively low (0-21.6%) resistance to clarithromycin, amikacin, bedaquiline, rifabutin, streptomycin, and clofazimine, and the resistant rates to isoniazid, rifampin, linezolid, doxycycline, and ethionamide were very high (72.1-100%). In addition, M. avium had a significantly higher resistance rate than that of M. intracellulare for ethambutol (92.3% vs 40.7%, P < 0.001), amikacin (15.4% vs 1.2%, P = 0.049), and cycloserine (69.2% vs 25.9%, P = 0.004). CONCLUSIONS: Our results supported the current usage of macrolides, rifabutin, and aminoglycosides in the regimens for MAC infection, and also demonstrated the low resistance rate against new drugs, such as clofazimine, tedizolid, and bedaquiline, suggesting the possible implementation of these drugs in MAC treatment.
Assuntos
Anti-Infecciosos , Infecção por Mycobacterium avium-intracellulare , Idoso , Amicacina/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Claritromicina/farmacologia , Clofazimina/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Rifabutina/farmacologiaRESUMO
OBJECTIVES: Our aim was to identify the pharmacokinetic/pharmacodynamic parameters of minocycline in the hollow-fibre system (HFS) model of pulmonary Mycobacterium avium complex (MAC) and to identify the optimal clinical dose. METHODS: Minocycline MICs for 55 MAC clinical isolates from the Netherlands were determined. We also co-incubated primary isolated macrophages infected with MAC with minocycline. Next, we performed a 28 day HFS-MAC model dose-response study in which we mimicked pulmonary concentration-time profiles achieved in patients. The HFS-MAC model was sampled at intervals to determine the minocycline pharmacokinetics and MAC burden. We identified the AUC0-24/MIC ratios associated with 1.0 log10 cfu/mL kill below day 0 (stasis), defined as a bactericidal effect. We then performed 10000 Monte Carlo experiments to identify the optimal dose for a bactericidal effect in patients. RESULTS: The MIC for 50% and 90% of cumulative clinical isolates was 8 and 64 mg/L, respectively. Minocycline decreased MAC bacterial burden below stasis in primary isolated macrophages. In the HFS-MAC model, minocycline achieved a microbial kill of 3.6 log10 cfu/mL below stasis. The AUC0-24/MIC exposure associated with a bactericidal effect was 59. Monte Carlo experiments identified a minocycline susceptibility MIC breakpoint of 16 mg/L. At this proposed breakpoint, the clinical dose of 200 mg/day achieved the bactericidal effect exposure target in â¼50% of patients, while 400 mg/day achieved this in 73.6% of patients, in Monte Carlo experiments. CONCLUSIONS: Minocycline at a dose of 400 mg/day is expected to be bactericidal. We propose a clinical trial for validation.
Assuntos
Teorema de Bayes , Minociclina/uso terapêutico , Modelos Biológicos , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Algoritmos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Linhagem Celular , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Testes de Sensibilidade Microbiana , Minociclina/farmacologia , Método de Monte CarloRESUMO
Mycobacterium aviumcomplex is now the leading mycobacterial cause of chronic pneumonia in the United States. Macrolides and ethambutol form the backbone of the regimen used in the treatment of pulmonary disease. However, therapy outcomes remain poor, with microbial cure rates of 4% in cavitary disease. The treatment dose of azithromycin has mostly been borrowed from that used to treat other bacterial pneumonias; there are no formal dose-response studies in pulmonaryM. aviumdisease and the optimal dose is unclear. We utilized population pharmacokinetics and pharmacokinetics/pharmacodynamics-derived azithromycin exposures associated with optimal microbial kill or resistance suppression to perform 10,000 patient Monte Carlo simulations of dose effect studies for daily azithromycin doses of 0.5 to 10 g. The currently recommended dose of 500 mg per day achieved the target exposures in 0% of patients. Exposures associated with optimal kill and resistance suppression were achieved in 87 and 54% of patients, respectively, only by the very high dose of 8 g per day. The azithromycin susceptibility breakpoint above which patients failed therapy on the very high doses of 8 g per day was an MIC of 16 mg/liter, suggesting a critical concentration of 32 mg/liter, which is 8-fold lower than the currently used susceptibility breakpoint of 256 mg/liter. If the standard dose of 500 mg a day were used, then the critical concentration would fall to 2 mg/liter, 128-fold lower than 256 mg/liter. The misclassification of resistant isolates as susceptible could explain the high failure rates of current doses.
Assuntos
Antibacterianos/farmacocinética , Azitromicina/farmacocinética , Farmacorresistência Bacteriana/efeitos dos fármacos , Modelos Estatísticos , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Antibacterianos/sangue , Antibacterianos/uso terapêutico , Área Sob a Curva , Azitromicina/sangue , Azitromicina/uso terapêutico , Simulação por Computador , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Complexo Mycobacterium avium/efeitos dos fármacos , Complexo Mycobacterium avium/crescimento & desenvolvimento , Infecção por Mycobacterium avium-intracellulare/sangue , Infecção por Mycobacterium avium-intracellulare/microbiologiaRESUMO
We developed, evaluated, and implemented a Taqman multiplex real-time polymerase chain reaction (PCR) assay for the detection of Mycobacterium avium complex (MAC), targeting the 16S-23S rRNA internal transcribed spacer, which we have combined with an existing Mycobacterium tuberculosis complex assay for use directly in clinical respiratory specimens. Evaluation of the performance of this assay for MAC detection included 464 clinical respiratory specimens tested prospectively. This real-time PCR assay was found overall to have a sensitivity of 71.1%, a specificity of 99.5%, a positive predictive value of 98.0%, and a negative predictive value of 90.2% for MAC. The assay provides results prior to the availability of cultured material and identification, most within 24 h of specimen receipt, and may reduce the need to culture MAC-PCR-positive specimens when susceptibility testing is not requested. Additionally, we have found significant cost savings of approximately $21.00 per specimen and staff time reductions of 3.75 h per specimen with implementation of this assay.
Assuntos
DNA Bacteriano/genética , Complexo Mycobacterium avium/genética , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/microbiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Líquido da Lavagem Broncoalveolar/microbiologia , Redução de Custos , Humanos , Técnicas de Sonda Molecular/economia , Tipagem Molecular/economia , Tipagem Molecular/métodos , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Sensibilidade e Especificidade , Escarro/microbiologia , Fatores de TempoRESUMO
The purpose of this investigation was to assess the usefulness of mycobacteremia detection in human immunodeficiency virus (HIV) patients with suspected tuberculosis. The study included 47 patients with suspected tuberculosis and confirmed HIV infection. A first blood sample was incubated in a BACTEC 9050 MB system, while white blood cells isolation was performed on a second blood specimen before incubation in a BACTEC MGIT 960 system. The third specimen was taken from the affected organs of each patient according to their clinical profile. Twelve (25.5%) patients were positive for mycobacterial infection identified by any of the methods used. Ten (21.2%) were positive for Mycobacterium tuberculosis and 2 (4.3%) for M. avium. Six patients were diagnosed by the culture of specimen from affected organs only, whilst three other patients were positive exclusively for blood cultures. Three additional patients were diagnosed by both methods. Four patients with negative cultures were ultimately diagnosed with tuberculosis by measuring the adenosine deaminase levels. Mycobacteremia detection can be used to increase the sensitivity of the diagnosis of tuberculosis and other mycobacteria in patients with HIV. However, it cannot be used as the sole diagnostic method. Clinical specimen cultures do not provide 100% diagnostic accuracy and it is, therefore, critical to further improve the mycobacteria detection sensitivity.
Assuntos
Técnicas Bacteriológicas , Infecções por HIV/complicações , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/complicações , Tuberculose/diagnóstico , Adenosina Desaminase/metabolismo , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Humanos , Infecção por Mycobacterium avium-intracellulare/complicações , Infecção por Mycobacterium avium-intracellulare/microbiologia , Sensibilidade e Especificidade , Tuberculose/microbiologiaAssuntos
Antituberculosos/administração & dosagem , Etambutol/administração & dosagem , Obesidade/tratamento farmacológico , Antituberculosos/farmacocinética , Antituberculosos/uso terapêutico , Relação Dose-Resposta a Droga , Resistência Microbiana a Medicamentos , Etambutol/farmacocinética , Etambutol/uso terapêutico , Humanos , Método de Monte Carlo , Mycobacterium avium/efeitos dos fármacos , Mycobacterium avium/patogenicidade , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologiaRESUMO
Organisms of the Mycobacterium avium-intracellulare complex (MAC) have been demonstrated to be susceptible to moxifloxacin. However, clinical data on how to utilize moxifloxacin to treat disseminated MAC are scanty. In addition, there have been no moxifloxacin pharmacokinetic-pharmacodynamic (PK/PD) studies performed for MAC infection. We utilized an in vitro PK/PD model of intracellular MAC to study moxifloxacin PK/PD for disseminated disease. Moxifloxacin doses, based on a serum half-life of 12 h, were administered, and the 0- to 24-h area under the concentration-time curve (AUC(0-24)) to MIC ratios associated with 1.0 log(10) CFU/ml per week kill and 90% of maximal kill (EC(90)) were identified. The AUC(0-24)/MIC ratio associated with 1.0 log(10) CFU/ml kill was 17.12, and that with EC(90) was 391.56 (r(2) = 0.97). Next, the moxifloxacin MIC distribution in 102 clinical isolates of MAC was identified. The median MIC was 1 to 2 mg/liter. Monte Carlo simulations of 10,000 patients with disseminated MAC were performed to determine the probability that daily moxifloxacin doses of 400 and 800 mg/day would achieve or exceed 1.0 log(10) CFU/ml per week kill or EC(90). Doses of 400 and 800 mg/day achieved the AUC(0-24)/MIC ratio of 17.12 in 64% and 92% of patients, respectively. The critical concentration of moxifloxacin against MAC was identified as 0.25 mg/liter in Middlebrook media. The proposed susceptibility breakpoint means that a larger proportion of clinical isolates is resistant to moxifloxacin prior to therapy. For patients infected with susceptible isolates, however, 800 mg a day should be examined for safety and efficacy for disseminated M. avium disease.
Assuntos
Antibacterianos/farmacologia , Antibacterianos/farmacocinética , Compostos Aza/farmacologia , Compostos Aza/farmacocinética , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Quinolinas/farmacologia , Quinolinas/farmacocinética , Antibacterianos/administração & dosagem , Área Sob a Curva , Compostos Aza/administração & dosagem , Linhagem Celular , Contagem de Colônia Microbiana , Fluoroquinolonas , Meia-Vida , Humanos , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Modelos Biológicos , Método de Monte Carlo , Moxifloxacina , Infecção por Mycobacterium avium-intracellulare/metabolismo , Infecção por Mycobacterium avium-intracellulare/microbiologia , Ligação Proteica , Quinolinas/administração & dosagemRESUMO
Ethambutol, together with a macrolide, is the backbone for treatment of disseminated Mycobacterium avium disease. However, at the standard dose of 15 mg/kg of body weight/day, ethambutol efficacy is limited. In addition, susceptibility breakpoints have consistently failed to predict clinical outcome. We performed dose-effect studies with extracellular M. avium as well as with bacilli within human macrophages. The maximal kill rate (E(max)) for ethambutol against extracellular bacilli was 5.54 log(10) CFU/ml, compared to 0.67 log(10) CFU/ml for intracellular M. avium, after 7 days of exposure. Thus, extracellular assays demonstrated high efficacy. We created a hollow-fiber system model of intracellular M. avium and performed microbial pharmacokinetic-pharmacodynamic studies using pharmacokinetics similar to those of ethambutol for humans. The E(max) in the systems was 0.79 log(10) CFU/ml with 7 days of daily therapy, so the kill rates approximated those encountered in patients treated with ethambutol monotherapy. Ratio of peak concentration to MIC (C(max)/MIC) was linked to microbial kill rate. The C(max)/MIC ratio needed to achieve the 90% effective concentration (EC(90)) in serum was 1.23, with a calculated intramacrophage C(max)/MIC ratio of 13. In 10,000 patient Monte Carlo simulations, doses of 15, 50, and 75 mg/kg achieved the EC(90) in 35.50%, 76.81%, and 86.12% of patients, respectively. Therefore, ethambutol doses of >or=50 mg/kg twice a week would be predicted to be better than current doses of 15 mg/kg for treatment of disseminated M. avium disease. New susceptibility breakpoints and critical concentrations of 1 to 2 mg/liter were identified for the determination of ethambutol-resistant M. avium in Middlebrook broth. Given that the modal MIC of clinical isolates is around 2 mg/liter, most isolates should be considered ethambutol resistant.
Assuntos
Antituberculosos/farmacocinética , Etambutol/farmacocinética , Macrófagos/microbiologia , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Mycobacterium avium/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Resistência Microbiana a Medicamentos , Humanos , Macrófagos/citologia , Testes de Sensibilidade Microbiana , Modelos Biológicos , Método de Monte Carlo , Mycobacterium avium/crescimento & desenvolvimento , Infecção por Mycobacterium avium-intracellulare/microbiologiaRESUMO
Recent studies suggest an increasing prevalence of pulmonary nontuberculous mycobacteria (NTM) disease. In the absence of prevalence and cost data, the public health burden of pulmonary NTM disease is difficult to assess. The goal of this study was to assess costs associated with NTM disease treatment and to identify risk factors associated with increased costs. Records from subjects with pulmonary NTM disease enrolled in a natural history protocol were abstracted for presenting symptoms, comorbidities, microbiology, and treatment histories. Antibiotic frequency, duration, adverse reaction, and costs were noted, the total antibiotic burden and cost were calculated, and risk factors associated with high costs were analyzed. From Jan 2004 to Dec 2005, 33 subjects were enrolled; 27 met disease criteria and had sufficient data to assess antibiotic use. Mycobacterium avium complex was present in 89% and Mycobacterium abscessus was present in 21% of subjects. Subjects received a median of 5 (1-10) antibiotics. Adverse effects were common seen in up to 50% with common antibiotics and up to 100% with uncommonly used antibiotics. Median burden of treatment was 2638 (84-7689) drug-days and the median total cost per patient was $19,876 ($398-70,917). Subjects with high treatment costs had an adjusted 9.5 fold (95% CI 1.5-97.2) likelihood of having M. abscessus and a 4.2 fold (95% CI 0.6-59.3) increased likelihood of having more extensive disease. Pulmonary NTM represent an underappreciated disease burden in the US population, with an associated treatment cost comparable to that for other chronic diseases of infectious origin such as HIV/AIDS.
Assuntos
Antibacterianos/uso terapêutico , Custos de Cuidados de Saúde , Pneumopatias/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/economia , Doença Crônica/tratamento farmacológico , Doença Crônica/economia , Feminino , Humanos , Pneumopatias/economia , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Infecção por Mycobacterium avium-intracellulare/economia , Infecção por Mycobacterium avium-intracellulare/microbiologia , Guias de Prática Clínica como Assunto , Fatores de RiscoRESUMO
From July 1995 to August 1998, mycobacterial blood cultures were obtained from 1032 HIV-infected patients seen at the Centro de Referência e Treinamento de AIDS (CRTA), Hospital São Paulo (HSP), and Centro de Referência de AIDS de Santos (CRAS). Overall, 179 episodes of mycobacteraemia were detected: 111 (62.0%) at CRTA, 50 (27.9%) at HSP, and 18 (10.1%) at CRAS. The frequency of positive cultures declined sharply from 22.6% in 1995 to 6.9% in 1998, consistent with the decrease in opportunistic infections following the publicly funded distribution of highly active antiretroviral therapy. In 1995, mycobacteraemia was more frequently due to Mycobacterium avium complex (59.2%) than Mycobacterium tuberculosis (28.6%), whereas in 1998 the relative frequencies were reversed (28.6 vs. 64.3% respectively), probably justified by the increased virulence of M. tuberculosis and the greater risk of invasive infection in less-immunocompromised patients, including patients unaware they are infected with HIV.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , HIV-1 , Infecção por Mycobacterium avium-intracellulare/epidemiologia , Infecção por Mycobacterium avium-intracellulare/microbiologia , Tuberculose/epidemiologia , Tuberculose/microbiologia , Saúde da População Urbana/estatística & dados numéricos , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade/economia , Terapia Antirretroviral de Alta Atividade/tendências , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Técnicas Bacteriológicas/métodos , Técnicas Bacteriológicas/tendências , Brasil/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Incidência , Mycobacterium/classificação , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Vigilância da População , Fatores de Risco , Sorotipagem , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológicoRESUMO
Mycobacterial catalases have been suggested as acting as virulence factors by protecting intracellular mycobacteria from reactive oxidative metabolites produced by host phagocytes. Mycobacterium intracellulare, like many other mycobacteria, produces two proteins with catalase activity: a heat-stable catalase (KatE) and an inducible, heat-labile catalase peroxidase (KatG). The M. intracellulare katG gene was cloned, and a plasmid derivative with a 4 bp insertion in the katG coding sequence was constructed and used for site-directed mutagenesis of M. intracellulare 1403 (ATCC 35761). The resulting katG mutant was highly resistant to isoniazid (INH), showed an increased sensitivity to H2O2 and had lost peroxidase and heat-sensitive catalase activity but retained heat-stable catalase activity. The plasmid carrying the katG frameshift allele was also used for mutagenesis of the mouse virulent M. intracellulare isolate D673. After intravenous injection into BALB/c mice, D673 and the isogenic katG mutant showed the same growth kinetics in the spleen, liver and lungs of the infected mice. Our results demonstrate that the KatG catalase peroxidase mediates resistance to H2O2 and susceptibility to INH but is not an essential virulence factor for the survival and growth of M. intracellulare in the mouse.
Assuntos
Proteínas de Bactérias , Genes Bacterianos , Complexo Mycobacterium avium/genética , Complexo Mycobacterium avium/patogenicidade , Peroxidases/genética , Animais , Antituberculosos/farmacologia , Sequência de Bases , Clonagem Molecular , Sondas de DNA/genética , Resistência Microbiana a Medicamentos/genética , Estabilidade Enzimática , Feminino , Humanos , Peróxido de Hidrogênio/farmacologia , Isoniazida/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Mutagênese Sítio-Dirigida , Complexo Mycobacterium avium/enzimologia , Infecção por Mycobacterium avium-intracellulare/etiologia , Infecção por Mycobacterium avium-intracellulare/microbiologia , Peroxidases/metabolismo , VirulênciaRESUMO
Laboratory testing is a prerequisite to predictions about the potential value of human clinical trials--the gold standard for the assessment of new therapies for infection with the Mycobacterium avium complex (MAC). These laboratory assessments must be made in the proper sequence, with appropriate models and methodology used to obtain data valid in determining whether clinical trials are warranted. In vitro testing permits measurements of minimal inhibitory and minimal bactericidal concentrations, identification of the synergism or antagonism of various agents, definition of an agent's pharmacokinetic properties (e.g., hydrophilicity or lipophilicity), and evaluation of a drug's intracellular penetration and activity against intracellular organisms. The most appropriate animal model for in vivo testing of activity against MAC is the beige mouse. Experiments in this model provide important data on an agent's minimal effective dose and on its optimal dose, dosing frequency, and route(s) of administration. Evaluations in the beige mouse also document whether the agent is bactericidal or bacteriostatic, whether it selects drug-resistant mutants, and whether its use in combination with other agents is beneficial.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antibacterianos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Animais , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Meios de Cultura , Modelos Animais de Doenças , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Testes de Sensibilidade Microbiana , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/microbiologiaRESUMO
For 273 patients evaluated for disseminated Mycobacterium avium complex infection, a total of 1,047 mycobacterial blood cultures (MBCs) were submitted; the M. avium complex was recovered from 140 (13%) of the specimens. Results for the paired MBCs were highly concordant: in 392 of 462 (85%) culture sets, both MBCs were negative, in 53 of 462 (11%) sets, both MBCs were positive, and in only 17 of 462 (4%) sets was one culture positive and the other negative. Acid-fast smears were done on sediments from 671 specimens; smears were positive for 4 of 98 (4%) cultures that grew the M. avium complex. A single MBC should be obtained and then repeated if negative and disseminated M. avium complex infection is still clinically suspected. Use of direct acid-fast smears of sediments is not a reliable means of detecting mycobacteremia.