RESUMO
Vancomycin-intermediate Staphylococcus aureus (VISA) infections are an emerging problem and antibiotic options are limited. We report the first case, to our knowledge, of heteroresistant VISA mediastinitis and bacteremia in a patient with a ventricular assist device who underwent orthotopic heart transplantation with clinical cure.
Assuntos
Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Transplante de Coração , Mediastinite/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Adulto , Aminoglicosídeos/farmacologia , Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Bacteriemia/cirurgia , Desbridamento , Desfibriladores Implantáveis , Feminino , Coração Auxiliar/efeitos adversos , Coração Auxiliar/microbiologia , Humanos , Lipoglicopeptídeos , Mediastinite/microbiologia , Mediastinite/cirurgia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/cirurgia , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Resistência a VancomicinaRESUMO
The agar proportion method (APM) for determining Mycobacterium tuberculosis susceptibilities is a qualitative method that requires 21 days in order to produce the results. The Sensititre method allows for a quantitative assessment. Our objective was to compare the accuracy, time to results, and ease of use of the Sensititre method to the APM. 7H10 plates in the APM and 96-well microtiter dry MYCOTB panels containing 12 antibiotics at full dilution ranges in the Sensititre method were inoculated with M. tuberculosis and read for colony growth. Thirty-seven clinical isolates were tested using both methods and 26 challenge strains of blinded susceptibilities were tested using the Sensititre method only. The Sensititre method displayed 99.3% concordance with the APM. The APM provided reliable results on day 21, whereas the Sensititre method displayed consistent results by day 10. The Sensititre method provides a more rapid, quantitative, and efficient method of testing both first- and second-line drugs when compared to the gold standard. It will give clinicians a sense of the degree of susceptibility, thus, guiding the therapeutic decision-making process. Furthermore, the microwell plate format without the need for instrumentation will allow its use in resource-poor settings.
Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/isolamento & purificação , Sensibilidade e Especificidade , Fatores de Tempo , Tuberculose/microbiologiaAssuntos
Herpesvirus Humano 1 , Erupção Variceliforme de Kaposi/diagnóstico , Dor/diagnóstico , Adulto , Antivirais/uso terapêutico , Exantema/virologia , Feminino , Humanos , Erupção Variceliforme de Kaposi/tratamento farmacológico , Erupção Variceliforme de Kaposi/patologia , Dor/tratamento farmacológico , Dor/patologiaRESUMO
The Sherlock Mycobacteria Identification HPLC system correctly identified to the species level 61 (67.8%) of 90 isolates growing on solid media, and 73 (45.3%) of 161 isolates directly from positive VersaTREK Myco bottles. When these data were re-analysed with a revised database, correct identifications increased to 91.1% and 83.2%, respectively. All Mycobacterium tuberculosis isolates were identified correctly, regardless of the inoculum source or database used. The use of the revised database with isolates obtained directly from positive VersaTREK Myco bottles allows the identification of most isolates within clinically relevant time-frames.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Mycobacterium/classificação , Meios de Cultura , Humanos , Mycobacterium/isolamento & purificação , Infecções por Mycobacterium/microbiologia , Reconhecimento Automatizado de PadrãoRESUMO
Rothia dentocariosa is a gram-positive rod found commonly as part of the normal flora of the mouth. It rarely causes clinical disease. Subacute infective endocarditis has been the most commonly reported R dentocariosa infection, and extracardiac complications occur frequently. Solitary intracranial hemorrhages have been reported in two cases. We describe the first case of infective endocarditis complicated by the sequential and unusually prolonged development of multiple new intracranial hemorrhages.
Assuntos
Actinomyces , Actinomicose/complicações , Actinomicose/microbiologia , Endocardite Bacteriana/complicações , Endocardite Bacteriana/microbiologia , Hemorragias Intracranianas/complicações , Nocardiose/complicações , Nocardiose/microbiologia , Actinomyces/classificação , Actinomicose/tratamento farmacológico , Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Fadiga/microbiologia , Febre/microbiologia , Humanos , Hemorragias Intracranianas/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mucosa Bucal/microbiologia , Nocardiose/tratamento farmacológico , Paresia/etiologiaRESUMO
OBJECTIVE: To evaluate the results of treating vancomycin-resistant Enterococcus faecium (VREF) bacteremia with chloramphenicol. METHODS: We retrospectively reviewed the charts of all adult patients with VREF bacteremia treated with chloramphenicol during the calendar year 1998 at a 522-bed tertiary referral center in New York City. Patients were identified by reviewing microbiology laboratory records. Patients with clinically significant VREF bacteremia who received chloramphenicol for at least 48 h were included in the study. Clinical and microbiological outcomes were determined. Microbiological and molecular tests were performed on a small representative sample of isolates to identify the presence of resistance mechanisms and to look for similarity among the isolates. RESULTS: Seven episodes of significant VREF bacteremia occurred in six patients. Mean age was 54 years. All patients had cancer and three had severe neutropenia. Five of seven episodes were associated with chronic indwelling devices, but in only one of these cases was the device removed. All isolates were susceptible to chloramphenicol in vitro. All six microbiologically evaluable episodes had a favorable response to chloramphenicol treatment, and four of seven (57%) clinically evaluable episodes had favorable outcomes. Only one death may have been due to VREF bacteremia, so the maximal attributable mortality was 14%. The three representative samples that were tested further were indistinguishable from one another and they displayed no evidence of resistance mechanisms. CONCLUSIONS: In a cohort of severely ill cancer patients, chloramphenicol was effective in treating VREF bacteremia. The use of chloramphenicol should be considered in treating infections with this highly resistant organism, where therapeutic options are limited.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Cloranfenicol/uso terapêutico , Enterococcus faecium/efeitos dos fármacos , Resistência a Vancomicina , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: To determine the pattern of penicillin use in the treatment of pneumococcal pneumonia, and factors contributing to the use of alternative antibiotics. METHODS: This study included all adult inpatients of St. Vincent's Hospital and Medical Center who had documented pneumococcal pneumonia between December 1998 and October 1999. St. Vincent's is a 600 bed tertiary teaching hospital in New York City. Patients who had Streptococcus pneumoniae isolated from a respiratory tract specimen were identified through microbiology laboratory records. A retrospective chart review of these patients was conducted, and those identified with clinical pneumonia were included in this study. Antibiotic use, patient demographics, resistance data, and clinician awareness of the antibiotic susceptibility results were noted. RESULTS: Sixty adult patients hospitalized with documented pneumococcal pneumonia were identified. Thirteen (21.6%) of the 60 patients received penicillin or ampicillin. Susceptibility results were not noted in the medical record in 21 (35.0%) of the 60 patients, and none received penicillin. High rates of reported penicillin allergy in 8 (13.3%) of the 60 patients, and reluctance to use penicillin when isolates demonstrated intermediate susceptibility in 8 (13.3%) of the 60 patients were observed. CONCLUSIONS: Several remediable obstacles to penicillin use were identified in this study. An increased awareness of susceptibility results by physicians and education of practitioners could have increased the use of penicillin as therapy to two-thirds of these patients.
Assuntos
Ampicilina/uso terapêutico , Penicilina G/uso terapêutico , Penicilinas/uso terapêutico , Pneumonia Pneumocócica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampicilina/efeitos adversos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Penicilina G/efeitos adversos , Resistência às Penicilinas , Penicilinas/efeitos adversos , Fatores de RiscoRESUMO
OBJECTIVE: To validate the non-radiometric, broth-based ESP system for determining Mycobacterium avium complex (MAC) susceptibilities. METHODS: MAC isolates from sterile body sites of 20 adult HIV-infected patients who were failing their present MAC regimen were identified. Susceptibilities were determined and comparisons made between the agar proportion method and the ESP system for clarithromycin, ethambutol, sparfloxacin and cycloserine. RESULTS: Ninety-nine percent of the MICS generated by the ESP system user identical to or lower than the MICs determined by the agar proportion METHOD: In vitro resistance was documented by the ESP system for 86% of the drugs that patients were taking at the time of breakthrough, and no resistance was seen to cycloserine, a drug that no patient was taking. CONCLUSIONS: The ESP system, a fast and reliable method for determining MAC susceptibilities, could be used to optimize MAC regimens in a timely fashion, avoid the use of ineffective drugs, minimize emerging resistance and ultimately improve outcome.
Assuntos
Complexo Mycobacterium avium/efeitos dos fármacos , Kit de Reagentes para Diagnóstico/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Resistência Microbiana a Medicamentos , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Testes de Sensibilidade Microbiana , Complexo Mycobacterium avium/crescimento & desenvolvimento , Infecção por Mycobacterium avium-intracellulare/complicações , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológicoRESUMO
A prospective study was undertaken to determine colonization rates, susceptibility profiles, and outcomes in patients with clinical isolates of Acinetobacter baumannii. Fifty percent of patients became colonized with A. baumannii, and 29% of these patients had clinical and colonizing isolates with discordant susceptibility profiles, without apparent relation to antibiotic use. Barrier infection control measures are necessary to prevent nosocomial transmission.
Assuntos
Acinetobacter/efeitos dos fármacos , Infecção Hospitalar/prevenção & controle , Acinetobacter/patogenicidade , Infecções por Acinetobacter/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecção Hospitalar/epidemiologia , Resistência Microbiana a Medicamentos , Feminino , Gastroenteropatias/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Estudos ProspectivosAssuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium scrofulaceum/crescimento & desenvolvimento , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Adulto , Humanos , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnósticoAssuntos
Infecções por Burkholderia/transmissão , Burkholderia cepacia/patogenicidade , Fibrose Cística/complicações , Transmissão de Doença Infecciosa do Paciente para o Profissional , Fibrose Cística/microbiologia , Pessoal de Saúde , Humanos , Saúde Ocupacional , Faringe/microbiologia , Roupa de ProteçãoAssuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Febre de Causa Desconhecida/etiologia , Micoses/complicações , Micoses/diagnóstico , Pancitopenia/complicações , Penicillium/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Medula Óssea/microbiologia , Diagnóstico Diferencial , Febre de Causa Desconhecida/complicações , Humanos , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológicoRESUMO
The purpose of this study was to review autopsy and gallium scan findings in two different acquired immune deficiency syndrome (AIDS) patient populations who had a confirmed diagnosis of tuberculosis (TB) to identify organs involved and accuracy of clinical diagnosis. The first group was comprised of 29 autopsies between January 1982 and December 1994, including only 18 patients who were diagnosed before death. Organs most commonly involved were the lymph nodes (59%), lungs (56%), spleen (53%), liver (45%), and kidneys (37%). Other opportunistic infections were present in 18 (59%) of autopsies, with more than one opportunistic infection present in 11 (37%) of the autopsies. Lungs were involved in 79% of all autopsies. The second population group included 94 patients with AIDS with a proven diagnosis of TB, only 24 of whom had gallium scans in the period between January 1992 and December 1994. Chest x-ray results were negative in 4 patients (17%); gallium scan results were positive in 16 patients (66%). The reasons for false-negative gallium scan results were due to anti-tuberculous treatment for periods varying from 2-21 months in 7 patients or the presence of extra pulmonary tuberculosis. The sites of TB involvement in the chest were: lung parenchyma in 5 patients (19%, 4 in mid and lower lung, and 1 in upper fields). There was lymph node involvement in all 16 patients (24 locations with mediastinal involvement in 23%, supraclavicular 23%, axillary 11%, retroperitoneal 11%, and inguinal region in 4%. We conclude that (1) tuberculosis in patients with AIDS behaves similar to primary tuberculosis; (2) the combination of chest x-ray and gallium imaging is sensitive for the diagnosis of pulmonary tuberculosis in patients with AIDS; (3) the involvement of mediastinal lymph nodes in gallium scans in the presence or absence of chest x-ray abnormalities should raise the possibility of TB involvement in patients with human immunodeficiency virus; (4) anti-TB treatment decreases the sensitivity of gallium scan.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/patologia , Radioisótopos de Gálio , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Tuberculose/patologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico por imagem , Síndrome da Imunodeficiência Adquirida/diagnóstico por imagem , Síndrome da Imunodeficiência Adquirida/patologia , Adulto , Antituberculosos/uso terapêutico , Autopsia , Axila/diagnóstico por imagem , Clavícula/diagnóstico por imagem , Reações Falso-Negativas , Feminino , Humanos , Canal Inguinal/diagnóstico por imagem , Masculino , Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Radiografia Torácica , Espaço Retroperitoneal/diagnóstico por imagem , Tuberculose/diagnóstico por imagem , Tuberculose Hepática/diagnóstico por imagem , Tuberculose Hepática/patologia , Tuberculose dos Linfonodos/diagnóstico por imagem , Tuberculose dos Linfonodos/patologia , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/patologia , Tuberculose Renal/diagnóstico por imagem , Tuberculose Renal/patologia , Tuberculose Esplênica/diagnóstico por imagem , Tuberculose Esplênica/patologiaRESUMO
Mycobacterial isolates were identified directly from positive ESP-Myco bottles by use of nucleic acid probes. Retrospective analysis of 360 cultures which grew either Mycobacterium tuberculosis, M. avium complex, or M. gordonae showed that 87% were identified by direct testing of an aliquot obtained at the time a positive culture was detected. Another 12% of these cultures gave results in the equivocal range, with only 1% of the isolates yielding negative results on initial testing.
Assuntos
Técnicas de Tipagem Bacteriana , Técnicas de Sonda Molecular , Mycobacterium/classificação , Técnicas de Tipagem Bacteriana/instrumentação , Mycobacterium/isolamento & purificaçãoRESUMO
SETTING: Incident patients with active tuberculosis (TB) resistant to two or more drugs in New York City hospitals in 1992. OBJECTIVE: To examine the New York-wide distribution of Public Health Research Institute (PHRI) strain W of Mycobacterium tuberculosis, an extremely drug-resistant strain identified by a 17-band Southern hybridization pattern using IS6110, during the peak tuberculosis year of 1992. We also compared strain W with other strains frequently observed in New York. DESIGN: Blinded retrospective study of stored M. tuberculosis cultures by restriction fragment length polymorphism (RFLP) DNA fingerprinting, and chart review. RESULTS: We found 112 cultures with the strain W fingerprint and 8 variants in 21 hospitals among incident patients hospitalized in 1992. Almost all isolates were resistant to four first-line drugs and kanamycin. This single strain made up at least 22% of New York City multiple-drug-resistant (MDR) TB in 1992, far more than any other strain. Almost all W-strain cases were acquired immune deficiency syndrome (AIDS) patients. The cluster is the most drug-resistant cluster identified in New York and the largest IS6110 fingerprint cluster identified anywhere to date. CONCLUSION: Because recommended four-drug therapy will not sterilise this very resistant strain, there was a city-wide nosocomial outbreak of W-strain TB in the early 1990s among New York AIDS patients. Other frequently seen strains were either also very resistant, or, surprisingly, pansusceptible. Individual MDR strains can be spread widely in situations where AIDS and TB are both common.
Assuntos
Surtos de Doenças/estatística & dados numéricos , Mycobacterium tuberculosis/classificação , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Idoso , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Técnicas de Tipagem Bacteriana , Resistência a Múltiplos Medicamentos , Feminino , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Cidade de Nova Iorque/epidemiologia , Estudos Retrospectivos , Especificidade da Espécie , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
A retrospective analysis of the files and Ga-67 scan findings of 32 AIDS patients with established diagnosis of disseminated Mycobacterium avium complex (MAC) was conducted in order to determine the sensitivity of Ga-67 scans for the diagnosis of this disease and the sites of MAC organ involvement. Fourteen of the 32 patients had early and delayed TI-201 scans that were also reviewed. Autopsy findings of AIDS patients in the 5 years (January 1990 to December 1994) were reviewed to determine the incidence and sites of involvement of disseminated MAC in AIDS autopsies. Chest x-ray was positive in only 41% of patients. Ga-67 scans were positive in 84% with multi-lymph node sites of involvement in 78% (hilar lymph nodes in 37.5%, supraclavicular 28.1% [all were on the left side], para-aortic 31.2%, paratracheal 18.2%, mediastinal nodes 6.2%, and axillary 3.1%), lung parenchymal in 18.7% and pleural in 9.3%). Increased uptake in the spleen in 16%, colitis 53.1% and enteritis 18.7%. Kaposi sarcoma in 9.3% and malignant lymphoma in 3.1%. TI-201 scans were only positive in 6 of 14 patients (42.8%). The autopsy data found the incidence of disseminated MAC in 23.7% (54 patients) out of a total of 228 autopsies. Approximately half of these cases (52%) were diagnosed antemortem. Other opportunistic infections were identified in 74%. The most common sites of MAC involvement were lymph nodes (74%), spleen (74%), liver (52%), lungs (22%), colon (13%), small bowel (11%), and bone marrow (9%). Associated Kaposi sarcoma was detected in 22% and non-Hodgkin's lymphoma in 13%. Problems in antemortem diagnosis were due to nonspecific presentations, involvement of intrathoracic and extrathoracic lymph nodes, liver, spleen and colon; and the higher incidence of opportunistic infections and negative chest x-ray in the majority of the patients.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico por imagem , Infecções Oportunistas Relacionadas com a AIDS/patologia , Radioisótopos de Gálio , Infecção por Mycobacterium avium-intracellulare/diagnóstico por imagem , Infecção por Mycobacterium avium-intracellulare/patologia , Radioisótopos de Tálio , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecção por Mycobacterium avium-intracellulare/epidemiologia , Cintilografia , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
A 29-year-old woman presented with clinical signs and symptoms of Acanthamoeba keratitis. Scanning slit confocal microscopy revealed a 26-mu-diameter object, resembling an Acanthamoeba cyst, in the anterior stroma. Numerous ovoid objects (possibly inflammatory cells, trophozoites, or altered keratocytes) were present. Normal keratocyte nuclei and the anterior corneal mosaic, readily imaged by scanning slit confocal microscopy of the normal cornea, were noticeably absent. Subsequent corneal biopsy confirmed the diagnosis of Acanthamoeba keratitis.
Assuntos
Ceratite por Acanthamoeba/patologia , Microscopia/métodos , Acanthamoeba/citologia , Ceratite por Acanthamoeba/etiologia , Adulto , Animais , Biópsia , Lentes de Contato Hidrofílicas/efeitos adversos , Substância Própria/parasitologia , Feminino , Humanos , Acuidade VisualRESUMO
OBJECTIVE: To describe 13 infections caused by Mycobacterium haemophilum. DESIGN: Identification of patients by microbiologic record review, followed by medical record review and a case-control study. SETTING: Seven metropolitan hospitals in New York. PATIENTS: All patients with M. haemophilum infections diagnosed between January 1989 and September 1991 and followed through September 1992. Surviving patients were enrolled in the case-control study. RESULTS: Infection with M. haemophilum causes disseminated cutaneous lesions, bacteremia, and diseases of the bones, joints, lymphatics, and the lungs. Improper culture techniques may delay laboratory diagnosis, and isolates may be identified incorrectly as other mycobacterial species. Persons with profound deficits in cell-mediated immunity have an increased risk for infection. These include persons with human immunodeficiency virus infection or lymphoma and those receiving medication to treat immunosuppression after organ transplant. Various antimycobacterial regimens have been used with apparent success to treat M. haemophilum infection. However, standards for defining antimicrobial susceptibility to the organism do not exist. CONCLUSIONS: Clinicians should consider this pathogen when evaluating an immunocompromised patient with cutaneous ulcerating lesions, joint effusions, or osteomyelitis. Microbiologists must be familiar with the fastidious growth requirements of this organism and screen appropriate specimens for mycobacteria using an acid-fast stain. If acid-fast bacilli are seen, M. haemophilum should be considered as the infecting organism as well as other mycobacteria, and appropriate media and incubation conditions should be used.
Assuntos
Hospedeiro Imunocomprometido , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Transplante de Medula Óssea/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium/isolamento & purificação , Mycobacterium/fisiologia , Infecções por Mycobacterium/tratamento farmacológico , Cidade de Nova Iorque/epidemiologiaRESUMO
The ability to provide susceptibility data for certain species of mycobacteria can be clinically useful. In this study, the disk elution method for susceptibility testing was adapted for testing ciprofloxacin against mycobacterial isolates. Of the 75 Mycobacterium tuberculosis isolates tested, including 23 multiply drug-resistant isolates, 96% were susceptible to ciprofloxacin at a breakpoint concentration of 2 micrograms/ml.