RESUMEN
Omadacycline is an aminomethylcycline antibiotic with in vitro activity against pathogens causing community-acquired bacterial pneumonia (CABP). This study investigated the activity of omadacycline against Legionella pneumophila strains isolated between 1995 and 2014 from nosocomial or community-acquired respiratory infections. Omadacycline exhibited extracellular activity similar to comparator antibiotics; intracellular penetrance was found by day 3 of omadacycline exposure. These results support the utility of omadacycline as an effective antibiotic for the treatment of CABP caused by L. pneumophila.
Asunto(s)
Antibacterianos/uso terapéutico , Legionella pneumophila/efectos de los fármacos , Enfermedad de los Legionarios/tratamiento farmacológico , Tetraciclinas/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Humanos , Legionella pneumophila/aislamiento & purificación , Pruebas de Sensibilidad MicrobianaRESUMEN
Moxifloxacin, a recent, new quinolone agent, has superior pharmacokinetics and appears to be safe for patients with renal failure, as it is mainly excreted in the bile. The case of a hemodialysis patient with Legionella pneumonia who was successfully treated with moxifloxacin is reported. A 76-year-old woman, who had been on hemodialysis for chronic renal failure secondary to diabetic nephropathy, visited her hospital with a cough and fever. Pneumonia was diagnosed, and intravenous administration of cefotiam hydrochloride was begun, but her respiratory condition deteriorated. She was transferred to our hospital with dyspnea. A chest radiograph showed consolidation in both lung fields and cardiomegaly. A urinary antigen test for Legionella was positive. Legionella pneumonia with heart failure was diagnosed and she was started on 400 mg a day moxifloxacin. Her clinical condition improved. Moxifloxacin appears to be useful in the treatment of Legionella pneumonia in patients with renal failure.
Asunto(s)
Antiinfecciosos/uso terapéutico , Compuestos Aza/uso terapéutico , Enfermedad de los Legionarios/tratamiento farmacológico , Neumonía Bacteriana/tratamiento farmacológico , Quinolinas/uso terapéutico , Diálisis Renal , Anciano , Femenino , Fluoroquinolonas , Humanos , MoxifloxacinoRESUMEN
Given the nonspecific clinical manifestations of Legionnaires' disease and the high mortality of untreated Legionnaires' disease, we recommend routine use of Legionella testing, especially the Legionella urinary antigen test, for all patients with community-acquired pneumonia. This includes patients with ambulatory pneumonia and hospitalized children. Legionella cultures should be more widely available, especially in hospitals where the drinking water is colonized with Legionella. Azithromycin or levofloxacin can be considered as first-line therapy. Other antibiotics including tetracyclines, tigecycline, other fluoroquinolones and other macrolides (especially clarithromycin) are also effective. The clinical response of quinolones may be somewhat more favorable compared to macrolides, but the outcome is similar. If the Legionnaires' disease is hospital-acquired, culturing of the hospital drinking water for Legionella is indicated.
Asunto(s)
Antibacterianos/uso terapéutico , Enfermedad de los Legionarios/tratamiento farmacológico , Animales , Antibacterianos/administración & dosificación , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Quimioterapia Combinada , Humanos , Legionella pneumophila/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Among infectious diseases, community-acquired pneumonia (CAP) is the leading cause of death in the United States and is associated with a substantial economic burden to the health care system. Initiating appropriate empiric therapy can be challenging given elevated resistance rates among Streptococcus pneumoniae strains. OBJECTIVE: To present current recommendations for management of CAP with respect to (a) choosing the appropriate site of care, and (b) antimicrobial selection based on bacterial etiology and the prevalence of resistance. SUMMARY: Mortality prediction tools, such as the PORT (Pneumonia Outcomes Research Team) Severity Index, CURB-65 (Confusion, Urea concentration, Respiratory rate, Blood pressure, and age>65), or CRB-65 (Confusion, Respiratory rate, Blood pressure, and age>65), can be invaluable in determining which CAP patients require hospitalization. These tools can help reduce overall costs for CAP by limiting hospitalizations of low-risk patients. S. pneumoniae remains the most common causative pathogen for CAP across all disease severities, and elevated rates of resistance to penicillin and macrolides can hinder selection of appropriate antimicrobial therapy. Antimicrobial resistance can impact clinical outcomes, including increasing the risk of treatment failure and breakthrough bacteremia. Current management guidelines recommend monotherapy with a respiratory fluoroquinolone or combination therapy with a beta-lactam and a macrolide (for patients admitted to the general medical ward) or with a beta-lactam and either a respiratory fluoroquinolone or a macrolide (for patients admitted to the intensive care unit [ICU] and who do not have risk factors for methicillin-resistant S. aureus or Pseudomonas). Optimized dosing regimens aim to ensure that pharmacokinetic and pharmacodynamic targets are met to achieve successful clinical outcomes and minimize resistance development. CONCLUSION: Effective management of patients with CAP requires selection of the proper site of care and appropriate empiric antimicrobial. Given the elevated rates of resistance among S. pneumoniae, local resistance patterns must be considered when choosing empiric therapy.
Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Fluoroquinolonas/uso terapéutico , Macrólidos/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , beta-Lactamas/uso terapéutico , Chlamydophila pneumoniae/aislamiento & purificación , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Quimioterapia Combinada , Humanos , Enfermedad de los Legionarios/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Guías de Práctica Clínica como Asunto , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
The in vitro and in vivo antibacterial activities of levofloxacin (LVFX), a quinolone antibacterial, against clinically isolated Legionella pneumophila were investigated in comparison with those of existing antimicrobial agents approved for legionnaires disease. The minimum inhibitory concentrations (MICs) of the agents against 42 strains of L. pneumophila isolated in Japan were determined using agar dilution methods with buffered starch yeast extract agar. MIC90 of LVFX was 0.03 microg/ml and this activity was similar to ciprofloxacin and pazufloxacin, and higher than telithromycin and minocycline. Therapeutic efficacy of LVFX was studied against a pneumonia model induced by intranasal of L. pneumophila strain suzuki serogoup 1 in DBA/2 mice. Therapeutic doses in mice were selected that would closely match human exposure profile, area under the concentration-time curve (AUC) for a human oral dose of LVFX at 500 mg once a day. LVFX decreased significantly the bacterial burden in the lungs from the next day of commencing treatment. These results, including in vitro antibacterial activity against clinical isolates and therapeutic efficacy of a humanized dosing regimen, provide good evidence to support the use of LVFX at 500 mg once a day for treating patient with legionnaires disease.
Asunto(s)
Antibacterianos/administración & dosificación , Modelos Animales de Enfermedad , Legionella pneumophila/crecimiento & desarrollo , Enfermedad de los Legionarios/tratamiento farmacológico , Enfermedad de los Legionarios/microbiología , Levofloxacino , Ofloxacino/administración & dosificación , Administración Oral , Animales , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Femenino , Legionella pneumophila/efectos de los fármacos , Legionella pneumophila/aislamiento & purificación , Ratones , Ratones Endogámicos DBA , Pruebas de Sensibilidad Microbiana , Ofloxacino/farmacología , Resultado del TratamientoRESUMEN
BACKGROUND: Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. However, limited data exist to validate this entity. We aimed to ascertain the epidemiology, causative organisms, antibiotic susceptibilities, and outcomes of and empirical antibiotic therapy for HCAP requiring hospitalization. METHODS: Observational analysis of a prospective cohort of nonseverely immunosuppressed hospitalized adults with pneumonia. Patients who had recent contact with the health care system through nursing homes, home health care programs, hemodialysis clinics, or prior hospitalization were considered to have HCAP. RESULTS: Of 727 cases of pneumonia, 126 (17.3%) were HCAP and 601 (82.7%) were community acquired. Compared with patients with community-acquired pneumonia, patients with HCAP were older (mean age, 69.5 vs 63.7 years; P < .001), had greater comorbidity (95.2% vs 74.7%; P < .001), and were more commonly classified into high-risk pneumonia severity index classes (67.5% vs 48.8%; P < .001). The most common causative organism was Streptococcus pneumoniae in both groups (27.8% vs 33.9%). Drug-resistant pneumococci were more frequently encountered in cases of HCAP. Legionella pneumophila was less common in patients with HCAP (2.4% vs 8.8%; P = .01). Aspiration pneumonia (20.6% vs 3.0%; P < .001), Haemophilus influenzae (11.9% vs 6.0%; P = .02), Staphylococcus aureus (2.4% vs 0%; P = .005), and gram-negative bacilli (4.0% vs 1.0%; P = .03) were more frequent in HCAP. Patients with HCAP more frequently received an initial inappropriate empirical antibiotic therapy (5.6% vs 2.0%; P = .03). The overall case-fatality rate (< 30 days) was higher in patients with HCAP (10.3% vs 4.3%; P = .007). CONCLUSIONS: At present, a substantial number of patients initially seen with pneumonia in the emergency department have HCAP. These patients require a targeted approach when selecting empirical antibiotic therapy.
Asunto(s)
Hospitalización , Factores de Edad , Anciano , Infecciones Comunitarias Adquiridas/microbiología , Comorbilidad , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Femenino , Humanos , Enfermedad de los Legionarios/tratamiento farmacológico , Enfermedad de los Legionarios/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Neumonía/tratamiento farmacológico , Neumonía/epidemiología , Neumonía/microbiología , Estudios Prospectivos , Índices de Gravedad del TraumaRESUMEN
BACKGROUND: Erythromycin (EM) and rifampicin (RFP) have mainly been used to treat patients with Legionella pneumonia. Since intravenous ciprofloxacin (CPFX) became available in Japan from 2000, many reports have been published detailing successful treatment of Legionella pneumonia with CPFX. In this study, we compared the evolution of patients with Legionella pneumonia treated with CPFX to those treated with EM. METHODS: The study included nine patients treated with CPFX and eighteen patients treated with EM. Diagnosis of these patients was made by culture, PCR, urinary antigen assay or a serological method. A comparison was made of the patients' characteristics, severity of pneumonia, efficacy of each agent and the clinical course. RESULTS: No significant differences were observed between the two groups, in regard to age, gender, underlying disease or severity of pneumonia. In addition, the period of time from onset of the disease until appropriate therapy did not differ significantly between the two groups. In the CPFX group, all of the patients were cured and in the EM group 16 out of the 18 patients were cured. Although there were no significant differences, the time to apyrexia, normalization of leukocytosis and a 50% decrease in C-reactive protein (CRP) occurred within a relatively shorter time frame in the CPFX group than in the EM group (3.5 versus 4 days, 4 versus 5.2 days, and 2.9 versus 10.3 days, respectively). And, the duration of antibiotic treatment in the CPFX group was significantly shorter than in the EM group. CONCLUSION: CPFX was as effective as erythromycin in the treatment of Legionella pneumonia. The effects of treatment may appear relatively earlier and the duration of treatment was significantly shorter in patients treated with CPFX therapy than with EM therapy.
Asunto(s)
Ciprofloxacina/administración & dosificación , Eritromicina/administración & dosificación , Enfermedad de los Legionarios/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Japón/epidemiología , Enfermedad de los Legionarios/diagnóstico , Enfermedad de los Legionarios/epidemiología , Masculino , Persona de Mediana Edad , Probabilidad , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
Following the first outbreaks of legionnaire's disease, erythromycin emerged as the treatment of choice without the foundation of rigorous clinical trials. The number of therapeutic failures with erythromycin, as well as the side-effects and drug interactions, led to the consideration of other drugs such as the new macrolides and quinolones for the treatment of legionnaire's disease in the 1990s. In this article, 19 studies in in-vitro intracellular models and seven animal studies that compared macrolides to quinolones were reviewed. Quinolones were found to have greater activity in intracellular models and improved efficacy in animal models compared with macrolides. No randomised trials comparing the clinical efficacy of the new macrolides and new quinolones have ever been performed. Three observational studies totalling 458 patients with legionnaire's disease have compared the clinical efficacy of macrolides (not including azithromycin) and quinolones (mainly levofloxacin). The results suggested that quinolones may produce a superior clinical response compared with the macrolides (erythromycin and clarithromycin) with regard to defervescence, complications, and length of hospital stay. Little data exist for direct comparison of quinolones and azithromycin.
Asunto(s)
Antiinfecciosos/uso terapéutico , Legionella pneumophila/efectos de los fármacos , Enfermedad de los Legionarios/tratamiento farmacológico , Quinolonas/uso terapéutico , Animales , Azitromicina/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Legionella pneumophila/crecimiento & desarrollo , Levofloxacino , Pruebas de Sensibilidad Microbiana , Ofloxacino/uso terapéuticoRESUMEN
Legionella species are ubiquitous in aquatic environments. About 50 years ago they entered the engineered (technical) environment, i.e. warm water systems with zones of stagnation. Since that time they represent a hygienic problem. After transmission to humans via aerosols legionellae might cause Legionella pneumonia (legionnaires' disease) or influenza-like respiratory infections (Pontiac fever). Epidemiological data suggest that Legionella strains might differ substantially in their virulence properties. Although the molecular basis is not understood L. pneumophila serogroup 1 especially MAb 3/1-positive strains cause the majority of infections. The main virulence feature is the ability to multiply intracellularly. After uptake into macrophages legionellae multiply in a specialized vacuole and finally lyse their host cells. Several bacterial factors like surface components, secretion systems and iron uptake systems are involved in this process. Since the clinical picture of Legionella pneumonia does not allow differentiation from pneumoniae caused by other pathogens, microbiological diagnostic methods are needed to establish the diagnosis. Cultivation of legionellae from clinical specimens, detection of antigens and DNA in patients' samples and detection of antibodies in serum samples are suitable methods. However, none of the diagnostic tests presently available offers the desired quality with respect to sensitivity and specificity. Therefore, the standard technique is to use several diagnostic tests in parallel. Advantages and disadvantages of the diagnostic procedures are discussed. Therapeutic options for Legionella infections are newer macrolides like azithromycin and chinolones (ciprofloxacin, levofloxacin and moxifloxacin).
Asunto(s)
Legionelosis , Antibacterianos/uso terapéutico , Anticuerpos Antibacterianos/análisis , Antígenos Bacterianos/análisis , Antígenos Bacterianos/orina , Compuestos Aza/uso terapéutico , Azitromicina/uso terapéutico , Ciprofloxacina/uso terapéutico , ADN Bacteriano/análisis , Diagnóstico Diferencial , Fluoroquinolonas , Humanos , Incidencia , Legionella/clasificación , Legionella/inmunología , Legionella/aislamiento & purificación , Legionella/patogenicidad , Legionella/fisiología , Legionella pneumophila/clasificación , Legionella pneumophila/inmunología , Legionella pneumophila/aislamiento & purificación , Legionella pneumophila/patogenicidad , Legionella pneumophila/fisiología , Legionelosis/diagnóstico , Legionelosis/tratamiento farmacológico , Legionelosis/epidemiología , Legionelosis/etiología , Legionelosis/microbiología , Enfermedad de los Legionarios/diagnóstico , Enfermedad de los Legionarios/tratamiento farmacológico , Enfermedad de los Legionarios/epidemiología , Enfermedad de los Legionarios/etiología , Enfermedad de los Legionarios/microbiología , Levofloxacino , Moxifloxacino , Ofloxacino/uso terapéutico , Reacción en Cadena de la Polimerasa , Quinolinas/uso terapéutico , Serotipificación , VirulenciaRESUMEN
Legionella pneumophila is an intracellularly-growing microorganism and the causative agent of Legionnaires' disease; this disease owes its name to the epidemic among American war veterans in Philadelphia in 1976. The analysis ofthe epidemic in Philadelphia revealed--retrospectively--that unlike beta-lactam antibiotica, erythromycin and tetracyclines provided protection against an unfavourable outcome. Despite the absence of prospective, blinded, randomised clinical trials, a well-founded choice for the antibiotic treatment of patients with a Legionella infection can be made using the evidence from in-vitro and cell culture studies, as well as studies in animal models. Although erythromycin, either or not in combination with rifampicin, is still recommended, there is not enough scientific evidence to support this as a first choice drug treatment. The available evidence suggests that quinolones (the most researched are ciprofloxacin and levofloxacin) are the treatment of choice in the case of severe Legionella pneumonia. Newer macrolides (especially azithromycin) have been shown to have some additional beneficial effect. However, the lack of an intravenous formulation limits the use of newer macrolides in severely ill patients.
Asunto(s)
Antibacterianos/uso terapéutico , Legionella pneumophila/efectos de los fármacos , Enfermedad de los Legionarios/tratamiento farmacológico , Eritromicina/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Tetraciclina/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: Community-acquired pneumonia is a common cause of morbidity and mortality throughout the world. Moxifloxacin, a new generation fluoroquinolone have become an attractive therapeutic alternative in the treatment of community-acquired pneumonia because of its excellent pharmacokinetic parameters and wide antimicrobial spectrum. AIMS: The authors reviewed the role of moxifloxacin in the treatment of community-acquired pneumonia based on their experience and the data of the literature. METHODS: The authors studied the clinical outcome of the patients treated with moxifloxacin due to community-acquired pneumonia in their hospital ward between May 1, 2002 and May 1, 2003. RESULTS: Four patients with pneumonia were treated ineffectively by moxifloxacin during a year. Serious clinical and radiological progression occurred to each patient despite moxifloxacin therapy, and two patients had to be admitted to intensive care unit. Three patients were successfully treated by 2nd or 3rd generation cephalosporin and clarithromycin, but one patient died. CONCLUSIONS: The authors call attention with these cases to the fact that in clinical trials oral moxifloxacin therapy was not more efficient either clinically or microbiologically than standard therapy in the treatment of community-acquired pneumonia. Moxifloxacin therapy is recommended to be reserved to patients allergic or not responsive to other antibiotics, and in the case of infections due to penicillin-resistant pneumococci.
Asunto(s)
Antibacterianos/uso terapéutico , Compuestos Aza/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Quinolinas/uso terapéutico , Adulto , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Femenino , Fluoroquinolonas , Humanos , Enfermedad de los Legionarios/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Moxifloxacino , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/diagnóstico por imagen , Radiografía , Resultado del TratamientoRESUMEN
BACKGROUND: Large outbreaks of Legionella pneumonia are rare, but when they occur provide an opportunity to assess predictors of mortality and efficacy of drug therapy. Although erythromycin has been the treatment of choice for many years, newer antimicrobials with increased activity against Legionella are available. A large outbreak of legionnaires' disease associated with the Melbourne Aquarium occurred in April 2000. AIM: To describe the patterns and impact of Legionella therapy, and predictors of outcome in a large group of hospitalized patients with legionnaires' disease. METHODS: A 6-month retrospective audit of hospitalized patients with proven legionnaires' disease around the time of the Melbourne Aquarium outbreak was conducted. Statistical analysis was performed using SAS version 8.0 (SAS Institute Inc., NC, USA). RESULTS: Data were obtained on 104 patients (71 aquarium related, 33 not related). There were six deaths (mortality rate 5.8%), three of which were attributable directly to progressive legionnaires' disease. The major predictors of death were pre-existing cardiac failure (P = 0.0035) and renal disease (P = 0.026). Erythro-mycin is still the most commonly used antibiotic (80% received i.v. erythromycin) with clinicians prescribing more than one active Legionella drug in the majority of cases (76%). Choice of initial antibiotic therapy did not statistically affect outcome as measured by death, length of hospital stay or time to defervescence, although there was a trend towards improved survival with i.v. erythromycin (P = 0.063). Intravenous erythromycin was associated with a 19% rate of phlebitis, whereas side-effects from other antibiotics were uncommon. CONCLUSION: The most commonly used Legionella therapy in Australia remains erythromycin. This continues to be an effective agent, however, side-effects are common.
Asunto(s)
Enfermedad de los Legionarios/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Ciprofloxacina/uso terapéutico , Comorbilidad , Brotes de Enfermedades , Eritromicina/uso terapéutico , Femenino , Humanos , Enfermedad de los Legionarios/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Roxitromicina/uso terapéutico , Resultado del Tratamiento , Victoria/epidemiologíaRESUMEN
The activity of the fluoroquinolone olamufloxacin (HSR-903) against Legionella spp. was studied in vitro and in vivo. The olamufloxacin MIC at which 50% of isolates are inhibited (MIC50) for 81 different Legionella spp. strains (59 type strains and 22 clinical isolates) was 0.008 mg/L, which was identical to sparfloxacin, whereas the MIC50s for erythromycin, levofloxacin and ciprofloxacin were 0.25, 0.032 and 0.032 mg/L, respectively. Olamufloxacin and sparfloxacin (at 0.008 mg/L) inhibited intracellular growth and subsequent cytotoxicity of L. pneumophila 80-045 in J774.1 macrophages, whereas levofloxacin and ciprofloxacin did not, at the same concentration. When olamufloxacin was given to the infected guinea pigs orally (5 mg/kg of body weight), peak levels in the lung were 3.02 mg/kg at 2 h post-administration, with a half-life of 3.41 h and an AUC0-12 of 12.31 mg.h/kg. The 2 day post-infection bacterial burden of the lung in the animals treated with olamufloxacin (5 and 1.25 mg/kg given orally twice a day) was much lower than in those treated with levofloxacin (same dose as olamufloxacin) or erythromycin (10 mg/kg given orally twice a day). When treated with olamufloxacin (5 mg/kg given orally twice a day) for 7 days, 11 of 12 L. pneumophila-infected guinea pigs survived for 14 days post-infection, as did all 12 guinea pigs treated with levofloxacin (5 mg/kg given orally twice a day) for 7 days. In contrast, only two of 12 animals treated with erythromycin survived and 10 of 11 died in the physiological saline group. Olamufloxacin was as effective as levofloxacin in a guinea pig model of Legionnaires' disease. These data warrant further study of whether olamufloxacin is an option for the treatment of Legionella infections.
Asunto(s)
Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Fluoroquinolonas/farmacología , Fluoroquinolonas/uso terapéutico , Legionella/efectos de los fármacos , Enfermedad de los Legionarios/tratamiento farmacológico , Quinolonas/farmacología , Quinolonas/uso terapéutico , Animales , Antibacterianos/farmacocinética , Área Bajo la Curva , Línea Celular , Eritromicina/uso terapéutico , Fluoroquinolonas/farmacocinética , Cobayas , Semivida , Enfermedad de los Legionarios/microbiología , Levofloxacino , Macrófagos/microbiología , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Ofloxacino/uso terapéutico , Quinolonas/farmacocinéticaAsunto(s)
Antibacterianos/uso terapéutico , Técnicas Bacteriológicas , Infecciones Comunitarias Adquiridas/diagnóstico , Neumonía Bacteriana/diagnóstico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/mortalidad , Humanos , Intubación Intratraqueal , Enfermedad de los Legionarios/diagnóstico , Enfermedad de los Legionarios/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/mortalidad , Infecciones por Pseudomonas/diagnóstico , Infecciones por Pseudomonas/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
The activities of tigecycline (Wyeth Research) against extracellular and intracellular Legionella pneumophila and for the treatment of guinea pigs with L. pneumophila pneumonia were studied. The tigecycline MIC at which 50% of strains are inhibited for 101 different Legionella sp. strains was 4 micro g/ml versus 0.125 and 0.25 micro g/ml for azithromycin and erythromycin, respectively. Tigecycline was about as active as erythromycin (tested at 1 micro g/ml) against the F889 strain of L. pneumophila grown in guinea pig alveolar macrophages and more active than erythromycin against the F2111 strain. Azithromycin (0.25 micro g/ml) was more active than (F889) or as active as (F2111) tigecycline (1 micro g/ml) in the macrophage model. When tigecycline was given (7.5 mg/kg of body weight subcutaneously once) to guinea pigs with L. pneumophila pneumonia, the mean peak serum and lung levels were 2.3 and 1.8 micro g/ml (1.2 and 1.5 micro g/g) at 1 and 2 h postinjection, respectively. The serum and lung areas under the concentration time curve from 0 to 24 h were 13.7 and 15.8 micro g. h/ml, respectively. Thirteen of 16 guinea pigs with L. pneumophila pneumonia treated with tigecycline (7.5 mg/kg subcutaneously once daily for 5 days) survived for 7 days post-antimicrobial therapy, as did 11 of 12 guinea pigs treated with azithromycin (15 mg/kg intraperitoneally once daily for 2 days). None of 12 guinea pigs treated with saline survived. Tigecycline-treated guinea pigs had average end of therapy lung counts of 1 x 10(6) CFU/g (range, 2.5 x 10(4) to 3.2 x 10(6) CFU/g) versus <1 x 10(2) CFU/g for azithromycin (range, undetectable to 100 CFU/g). A second guinea pig study examined the ability of tigecycline to clear L. pneumophila from the lung after 5 to 9 days of therapy; bacterial concentrations 1 day posttherapy ranged from log(10) 4.2 to log(10) 5.5 CFU/g for four different dosing regimens. Tigecycline is about as effective as erythromycin against intracellular L. pneumophila, but tigecycline inactivation by the test media confounded the interpretation of susceptibility data. Tigecycline was effective at preventing death from pneumonia in an animal model of Legionnaires' disease, warranting human clinical trials of the drug for the disease.
Asunto(s)
Modelos Animales de Enfermedad , Enfermedad de los Legionarios/tratamiento farmacológico , Minociclina/análogos & derivados , Minociclina/uso terapéutico , Animales , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Cobayas , Semivida , Legionella pneumophila/efectos de los fármacos , Masculino , Tasa de Depuración Metabólica , Pruebas de Sensibilidad Microbiana , Minociclina/farmacocinética , Minociclina/farmacología , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/microbiología , TigeciclinaRESUMEN
Even though cigarette smoking has been shown to suppress immune responses in the lungs, little is known about the effect of cigarette smoke components on respiratory infections. In the present study, the effects of cigarette smoke condensate (CSC) on bacterial replication in alveolar macrophages and the immune responses of macrophages to infection were examined. Furthermore, a possible immunotherapeutic effect of epigallocatechin gallate (EGCg), a major form of tea catechins, on the CSC-induced suppression of antimicrobial activity and immune responses of alveolar macrophages was also determined. The treatment of murine alveolar macrophage cell line (MH-S) cells with CSC significantly enhanced the replication of Legionella pneumophila in macrophages and selectively down-regulated the production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) induced by bacterial infection. The treatment of macrophages with EGCg not only overcame the CSC-induced suppression of antimicrobial activity but also strengthened the resistance of macrophages to infection. EGCg also markedly up-regulated the CSC-suppressed IL-6 and TNF-alpha production by macrophages in response to infection. The results of exogenous TNF-alpha treatment and neutralization treatment with anti-TNF-alpha and anti-gamma-interferon (IFN-gamma) antibodies and the determination of IFN-gamma mRNA levels indicate that CSC-suppressed macrophages can be activated by EGCg to inhibit L. pneumophila growth by up-regulation of TNF-alpha and IFN-gamma production. Thus, this study revealed that CSC selectively alters the immune responses of macrophages to L. pneumophila infection and leads to an enhancement of bacterial replication in macrophages. In addition, the tea catechin EGCg can diminish such suppressive effects of CSC on alveolar macrophages.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Catequina/análogos & derivados , Catequina/farmacología , Tolerancia Inmunológica/efectos de los fármacos , Inmunidad Celular/efectos de los fármacos , Enfermedad de los Legionarios/inmunología , Humo/efectos adversos , Adyuvantes Inmunológicos/uso terapéutico , Animales , Catequina/uso terapéutico , Línea Celular , Citocinas/efectos de los fármacos , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Legionella pneumophila/efectos de los fármacos , Legionella pneumophila/crecimiento & desarrollo , Enfermedad de los Legionarios/tratamiento farmacológico , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/metabolismo , Ratones , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Nicotiana/efectos adversosRESUMEN
We describe a patient with community-acquired pneumonia due to Legionella pneumophila serogroup 6. This patient was found to have bronchoalveolar carcinoma of the lung by means of cytologic testing in 1 of 2 bronchoalveolar lavage samples, but no lesions were visible on bronchoscopy. Despite intravenous administration of azithromycin to the patient, repeat culture and polymerase chain reaction showed persistence of Legionella; the isolates remained susceptible to azithromycin. The patient did not respond to 14 doses of daily intravenously administered azithromycin. The poor outcome may have been partially due to the suspected underlying lung malignancy, as shown by cytologic examination, and by a delay in seeking medical attention.
Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Enfermedad de los Legionarios/tratamiento farmacológico , Neumonía Bacteriana/tratamiento farmacológico , Anciano , Infecciones Comunitarias Adquiridas/diagnóstico por imagen , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/fisiopatología , Resultado Fatal , Femenino , Humanos , Legionella pneumophila/efectos de los fármacos , Legionella pneumophila/genética , Legionella pneumophila/aislamiento & purificación , Enfermedad de los Legionarios/diagnóstico por imagen , Enfermedad de los Legionarios/microbiología , Enfermedad de los Legionarios/fisiopatología , Pruebas de Sensibilidad Microbiana , Neumonía Bacteriana/diagnóstico por imagen , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/fisiopatología , Radiografía , Insuficiencia del TratamientoRESUMEN
The in vivo efficacy of trovafloxacin, intraperitoneally administered as alatrofloxacin (CP-116,517), was assessed and compared with that of erythromycin, alone or in combination with rifampicin, in a model of Legionella pneumophila pneumonia in guinea pigs. Trovafloxacin (5 mg/kg administered as alatrofloxacin once daily for 7 days) gave a survival rate of 100% in infected animals. Clearance of bacteria and of bacteria-induced lesions from lungs was achieved by day 6 post-inoculation. The lungs of trovafloxacin-treated animals remained free of bacteria at day 28 post-challenge. Trovafloxacin proved as effective as erythromycin administered intraperitoneally, but was superior to erythromycin alone. or in combination with rifampicin, when given orally.
Asunto(s)
Antiinfecciosos/uso terapéutico , Fluoroquinolonas , Enfermedad de los Legionarios/tratamiento farmacológico , Profármacos/uso terapéutico , Administración Oral , Animales , Antiinfecciosos/administración & dosificación , Antiinfecciosos/farmacología , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada/administración & dosificación , Quimioterapia Combinada/uso terapéutico , Eritromicina/administración & dosificación , Eritromicina/uso terapéutico , Femenino , Cobayas , Inyecciones Intraperitoneales , Legionella pneumophila/efectos de los fármacos , Enfermedad de los Legionarios/microbiología , Pulmón/microbiología , Pruebas de Sensibilidad Microbiana , Distribución Aleatoria , Rifampin/administración & dosificación , Rifampin/uso terapéuticoRESUMEN
The activity of six antibiotics directed against intracellularly multiplying Legionella pneumophilia was examined in tissue cultures with J774 macrophages. The drugs tested were the new quinolones, BAY Y 3118 and clinafloxacin, and ciprofloxacin, erythromycin, gentamicin and ampicillin served as reference drugs. Additionally, the MICs of these drugs against L. pneumophila were determined in vitro by broth microdilution. Despite their low MIC values, ampicillin and gentamicin did not inhibit intracellular multiplication of L. pneumophila in J774 macrophages. In contrast, an inhibition of intracellular growth could be demonstrated for the four other antibiotics. The new quinolones BAY Y 3118 and clinafloxacin showed the highest activity against intracellular L. pneumophila. At a concentration of 0.00078 mg/L already, a marked reduction in bacterial counts was seen for both drugs in comparison to the growth control without antibiotics. The corresponding effective concentrations were 0.0125 mg/L for ciprofloxacin and 0.2 mg/L for erythromycin. It may be concluded that new quinolone derivatives might become an alternative to erythromycin and rifampicin which at present are the drugs of primary choice for the treatment of legionnaires' disease.
Asunto(s)
Antiinfecciosos/uso terapéutico , Fluoroquinolonas , Legionella pneumophila/efectos de los fármacos , Enfermedad de los Legionarios/tratamiento farmacológico , Quinolonas/uso terapéutico , Ampicilina/farmacología , Ampicilina/uso terapéutico , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinfecciosos/farmacología , Técnicas Bacteriológicas , Ciprofloxacina/farmacología , Ciprofloxacina/uso terapéutico , Recuento de Colonia Microbiana , Eritromicina/farmacología , Eritromicina/uso terapéutico , Gentamicinas/farmacología , Gentamicinas/uso terapéutico , Legionella pneumophila/crecimiento & desarrollo , Macrófagos , Ratones , Penicilinas/farmacología , Penicilinas/uso terapéutico , Quinolonas/farmacología , Células Tumorales CultivadasRESUMEN
Legionella pneumophila is the cause of Legionnaires' disease, and Pontiac fever, an influenza-like condition without pneumonia. We present a case of Pontiac fever after exposure to a hot tub contaminated with L pneumophila. A 37 y/o wf presented to the office with acute onset of sore throat, fever, headache, and myalgia. Patient was hospitalized 3 days later because of worsening shortness of air. Chest x-ray was normal. Patient was treated with 2 days of IV erythromycin and was discharged home on oral erythromycin. Her Legionella IFA was 1:16,384. Two days later, she developed chest tightness, pleuritic chest pain, and increasing shortness of air but did not have any cough or sputum production. She was re-hospitalized with a diagnosis of Pontiac fever and treated with IV erythromycin plus oral rifampin. A repeat chest x-ray remained normal. After a detailed epidemiologic history was obtained, it was noted that she became ill after using a hot tub, which her two children also used and they themselves developed a self limited illness. Water from the hot tub was positive for L pneumophila by DFA, culture, and PCR. Patient improved gradually with therapy and was discharged home. This report emphasizes the importance of a complete epidemiologic history in the diagnosis of respiratory infections. It also demonstrates that aquatic environment can be contaminated with Legionella and serve as a source of infection.