RESUMEN
We have previously reported on the susceptibility and epidemiology of Clostridioides difficile isolates from six geographically dispersed medical centers in the United States. This current survey was conducted with isolates collected in 2020-2021 from six geographically dispersed medical centers in the United States, with specific attention to susceptibility to ridinilazole as well as nine comparators. C. difficile isolates or stools from patients with C. difficile antibiotic-associated diarrhea were collected and referred to a central laboratory. After species confirmation of 300 isolates at the central laboratory, antibiotic susceptibilities were determined by the agar dilution method [M11-A9, Clinical and Laboratory Standards Institute (CLSI)] against the 10 agents. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Ridinilazole had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL, and no isolate had an MIC greater than 0.5 mcg/mL. In comparison, fidaxomicin had an MIC 90 of 0.5 mcg/mL. The vancomycin MIC 90 was 2 mcg/mL with a 0.7% resistance rate [both CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria]. The metronidazole MIC 90 was 1 mcg/mL, with none resistant by CLSI criteria, and a 0.3% resistance rate by EUCAST criteria. Among the 50 different ribotypes isolated in the survey, the most common ribotype was 014-020 (14.0%) followed by 106 (10.3%), 027 (10%), 002 (8%), and 078-126 (4.3%). Ridinilazole maintained activity against all ribotypes and all strains resistant to any other agent tested. Ridinilazole showed excellent in vitro activity against C. difficile isolates collected between 2020 and 2021 in the United States, independent of ribotype.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Clostridioides difficile/genética , Clostridioides , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/epidemiología , Pruebas de Sensibilidad Microbiana , RibotipificaciónRESUMEN
BACKGROUND: Geographic and temporal trends in the distribution of PCR ribotypes for Clostridioides difficile associated diarrheal isolates obtained in the United States (US) are changing. As part of a US national surveillance program of C. difficile susceptibility to fidaxomicin, we quantified the distribution of PCR ribotypes of stool isolates collected from 2011 to 2016. METHODS: C. difficile isolates or C. difficile toxin + stools from patients with C. difficile infection (CDI) were submitted for testing to Tufts Medical Center from 6 geographically distinct medical centers. Following isolation and confirmation as C. difficile, approximately 35% of the isolates were randomly sampled, stratified by center, for PCR ribotyping by capillary gel electrophoresis. Toxin gene profiling was performed on all isolates. RESULTS: 939 isolates from a total of 2814 (33.4%) isolated over the 6 years were analyzed. Seventy unique ribotypes were observed, including 19 ribotypes observed 10 or more times. Sixteen ribotypes were not previously observed in our data base. Ribotype 027 declined by more than 60% over the 6 years of the survey from 35.3% to 13.1% (pâ¯<â¯0.001). Ribotype 106 was the most common in 2016, followed by 027 and 014-020. There were strong correlations between 027 and binary toxin with the 18 base pair deletion of tcdC and ribotype 078-126 had 100% concordance with the previously described tcdC 39 base pair deletion. CONCLUSIONS: The frequency of ribotypes in the US has changed with a marked decline in 027. Each of the geographical areas had variations which differed from each other, but collectively, these results suggest that the changing epidemiology of C. difficile in the US is consistent with what is being seen in Europe. Continued surveillance and monitoring of changes in ribotype distributions of C. difficile are warranted.
Asunto(s)
Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/epidemiología , Ribotipificación , Toxinas Bacterianas/genética , Técnicas de Tipificación Bacteriana/métodos , Diarrea/epidemiología , Europa (Continente)/epidemiología , Heces/microbiología , Genes Bacterianos , Humanos , ARN Ribosómico/genética , Estados Unidos/epidemiologíaRESUMEN
In 2011, we initiated a sentinel surveillance network to assess changes in Clostridioides (formerly Clostridium) difficile antimicrobial susceptibility to fidaxomicin from 6 geographically dispersed medical centers in the United States. This report summarizes data from 2013 to 2016. C. difficile isolates or toxin-positive stools from patients were referred to a central laboratory. Antimicrobial susceptibility was determined by agar dilution. CLSI, EUCAST, or FDA breakpoints were used, where applicable. Toxin gene profiles were characterized by multiplex PCR on each isolate. A random sample of approximately 40% of isolates, stratified by institution and year, was typed by restriction endonuclease analysis (REA). Among 1,889 isolates from 2013 to 2016, the fidaxomicin MIC90 was 0.5 µg/ml; all isolates were inhibited at ≤1 µg/ml. There were decreases in metronidazole and vancomycin MICs over time. Clindamycin resistance remained unchanged (27.3%). An increase in imipenem resistance was observed. By 2015 to 2016, moxifloxacin resistance decreased in all centers. The proportion of BI isolates decreased from 25.5% in 2011 to 2012 to 12.8% in 2015 to 2016 (P < 0.001). The BI REA group correlated with moxifloxacin resistance (BI 84% resistant versus non-BI 12.5% resistant). Fidaxomicin MICs have not changed among C. difficile isolates of U.S. origin over 5 years post licensure. There has been an overall decrease in MICs for vancomycin, metronidazole, moxifloxacin, and rifampin and an increase in isolates resistant to imipenem. Moxifloxacin resistance remained high among the BI REA group, but the proportion of BI isolates has decreased. Continued geographic variations in REA groups and antimicrobial resistance persist.
Asunto(s)
Antibacterianos/farmacología , Clostridioides difficile/efectos de los fármacos , Infecciones por Clostridium/microbiología , Diarrea/microbiología , Fidaxomicina/farmacología , ADP Ribosa Transferasas/genética , Proteínas Bacterianas/genética , Toxinas Bacterianas/genética , Clindamicina/farmacología , Clostridioides difficile/genética , Clostridioides difficile/aislamiento & purificación , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Enterotoxinas/genética , Humanos , Imipenem/farmacología , Pruebas de Sensibilidad Microbiana , Prohibitinas , Vigilancia de Guardia , Estados UnidosRESUMEN
New on-demand multiplex molecular respiratory viral diagnostics offer superior performance although can be expensive and some platforms cannot process multiple specimens simultaneously. We performed a retrospective study reviewing results of patients tested for respiratory viruses following introduction of a two-stage testing algorithm incorporating an initial screen with Sofia® immunoassay then secondary Biofire Filmarray®, and compared to a period when only Filmarray® was used. Of 2976 testing episodes, 1814 underwent initial Sofia® then follow-up FilmArray®. A diagnosis of influenza was made by Sofia® in 282 patients, and by FilmArray® in an additional 163 (median time to result 1.12hours versus 3.46hours, P<0.001). Significantly more patients received their diagnosis within 90minutes in winter despite testing more samples (11.1% versus 3.4%, P<0.001), and approximately $36,000 was saved. An algorithmic approach to respiratory viral diagnosis can combine the advantages of accuracy and speed and be cost saving.
Asunto(s)
Algoritmos , Pruebas Diagnósticas de Rutina/métodos , Inmunoensayo , Gripe Humana/diagnóstico , Gripe Humana/virología , Reacción en Cadena de la Polimerasa Multiplex , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Pruebas Diagnósticas de Rutina/economía , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Tamizaje Masivo/economía , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
AIM: To develop a novel validated method for the isolation of Bifidobacterium animalis ssp. lactis BB-12 (BB-12) from faecal specimens and apply it to studies of BB-12 and Lactobacillus rhamnosus GG (LGG) recovered from the healthy human gastrointestinal (GI) tract. METHODS AND RESULTS: A novel method for isolating and enumerating BB-12 was developed based on its morphologic features of growth on tetracycline-containing agar. The method identified BB-12 correctly from spiked stool close to 100% of the time as validated by PCR confirmation of identity, and resulted in 97-104% recovery of BB-12. The method was then applied in a study of the recovery of BB-12 and LGG from the GI tract of healthy humans consuming ProNutrients® Probiotic powder sachet containing BB-12 and LGG. Viable BB-12 and LGG were recovered from stool after 21 days of probiotic ingestion compared to baseline. In contrast, no organisms were recovered 21 days after baseline in the nonsupplemented control group. CONCLUSIONS: We demonstrated recovery of viable BB-12, using a validated novel method specific for the isolation of BB-12, and LGG from the GI tract of healthy humans who consumed the probiotic supplement. SIGNIFICANCE AND IMPACT OF THE STUDY: This method will enable more detailed and specific studies of BB-12 in probiotic supplements, including when in combination with LGG.
Asunto(s)
Bifidobacterium animalis/aislamiento & purificación , Tracto Gastrointestinal/microbiología , Lacticaseibacillus rhamnosus/fisiología , Probióticos/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos , Bifidobacterium animalis/clasificación , Bifidobacterium animalis/genética , Bifidobacterium animalis/fisiología , Suplementos Dietéticos , Heces/microbiología , Femenino , Voluntarios Sanos , Humanos , Lacticaseibacillus rhamnosus/genética , Lacticaseibacillus rhamnosus/aislamiento & purificación , Masculino , Persona de Mediana Edad , Tetraciclina , Adulto JovenRESUMEN
The susceptibility trends for Bacteroides fragilis and related species against various antibiotics were determined using data from 3 years of surveillance (2010-2012) on 779 isolates referred by 7 medical centers. The antibiotic test panel included imipenem, ertapenem, meropenem, ampicillin-sulbactam, piperacillin-tazobactam, cefoxitin, clindamycin, moxifloxacin, tigecycline, linezolid, chloramphenicol and . MICs were determined using the agar dilution CLSI reference method. Carbapenem resistance remained low (range 1.1%-2.5%) and unchanged from 2008 to 9 through 2010-2012. Resistance also remained low to the beta-lactam/beta-lactamase inhibitor combinations (1.1%-4.4%). While resistance to clindamycin and moxifloxacin remained high; rates were lower for B. fragilis in 2010-12 (24% and 19% respectively) compared to the earlier time frame of 2008-9 (29% and 35% respectively for the earlier time frame). There were notable species and resistance associations which have been demonstrated previously. No resistance to metronidazole or chloramphenicol resistance was seen. These data demonstrate the continued variability in resistance among Bacteroides and Parabacteroides species, but do demonstrate that carbapenems and beta-lactam/beta-lactamase inhibitor combinations remain very active throughout the United States.
Asunto(s)
Antiinfecciosos/farmacología , Infecciones por Bacteroides/tratamiento farmacológico , Bacteroidetes/efectos de los fármacos , Carbapenémicos/farmacología , Farmacorresistencia Microbiana , Inhibidores de beta-Lactamasas/farmacología , Bacteroides/efectos de los fármacos , Infecciones por Bacteroides/microbiología , Bacteroides fragilis/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/farmacología , Piperacilina/farmacología , Combinación Piperacilina y Tazobactam , Estados UnidosRESUMEN
In 2011 a surveillance study for the susceptibility to fidaxomicin and epidemiology of Clostridium difficile isolates in the United States was undertaken in seven geographically dispersed medical centers. This report encompasses baseline surveillance in 2011 and 2012 on 925 isolates. A convenience sample of C. difficile isolates or toxin positive stools from patients were referred to a central laboratory. Antimicrobial susceptibility was determined by agar dilution (CLSI M11-A8). Clinical and Laboratory Standards Institute (CLSI), Food and Drug Administration, or European Union of Clinical Antimicrobial Susceptibility Testing (EUCAST) breakpoints were applied where applicable. Toxin gene profiles were characterized by multiplex PCR on each isolate. A random sample of 322 strains, stratified by institution, underwent restriction endonuclease analysis (REA). The fidaxomicin MIC90 was 0.5 µg/ml for all isolates regardless of REA type or toxin gene profile, and all isolates were inhibited at ≤1.0 µg/ml. By REA typing, BI strains represented 25.5% of the isolates. The toxin gene profile of tcdA, tcdB, and cdtA/B positive with a tcdC 18-bp deletion correlated with BI REA group. Moxifloxacin and clindamycin resistance was increased among either BI or binary toxin-positive isolates. Metronidazole and vancomycin showed reduced susceptibility (EUCAST criteria) in these isolates. Geographic variations in susceptibility, REA group and binary toxin gene presence were observed. Fidaxomicin activity against C. difficile isolated in a national surveillance study did not change more than 1 year after licensure. This analysis provides baseline results for future comparisons.
Asunto(s)
Aminoglicósidos/farmacología , Antibacterianos/farmacología , Clostridioides difficile/efectos de los fármacos , Diarrea/epidemiología , Enterocolitis Seudomembranosa/epidemiología , Genes Bacterianos , Vigilancia de Guardia , Toxinas Bacterianas/genética , Toxinas Bacterianas/inmunología , Toxinas Bacterianas/aislamiento & purificación , Clindamicina/farmacología , Clostridioides difficile/genética , Clostridioides difficile/aislamiento & purificación , Diarrea/tratamiento farmacológico , Diarrea/microbiología , Farmacorresistencia Bacteriana/genética , Enterocolitis Seudomembranosa/tratamiento farmacológico , Enterocolitis Seudomembranosa/microbiología , Fidaxomicina , Fluoroquinolonas/farmacología , Humanos , Metronidazol/farmacología , Pruebas de Sensibilidad Microbiana , Moxifloxacino , Reacción en Cadena de la Polimerasa Multiplex , Prohibitinas , Estados Unidos/epidemiología , Vancomicina/farmacologíaRESUMEN
BACKGROUND AND OBJECTIVES: To evaluate standard intravenous immunoglobulin (IVIG) as an alternative to intravenous cytomegalovirus hyperimmune immunoglobulin (CMVIG) for prophylaxis and therapy of cytomegalovirus (CMV) disease, we measured the ELISA and neutralizing titres of CMV-specific antibodies in CMVIG and IVIG preparations. MATERIALS AND METHODS: Anti-CMV-IgG ELISA and neutralizing titres (fibroblast-based test) in CMVIG CG (Cytogam®, n = 20), CMVIG CT (Cytotect® CP, n = 3), IVIG P (Privigen®, n = 32) and IVIG K/G (Kiovig®/Gammagard®, n = 5) were compared, and IgG subclasses 1-4 were determined by nephelometry. RESULTS: Cytomegalovirus hyperimmune immunoglobulins contained more than fourfold higher CMV ELISA and CMV-neutralizing activity per gram of IgG than the standard IVIGs. Pooled data for all four products showed a significant correlation between anti-CMV-IgG ELISA and neutralizing titres (r = 0·93, P < 0·001). There was a good correlation between the IgG3 content and CMV-neutralizing antibodies amongst lots of CMVIGs (r = 0·91, P = 0·01), but this did not extend to the IVIGs. CMVIG CG contained the highest CMV-neutralizing activity (3497 ± 395 PEIU/g IgG) of any product tested. CONCLUSION: The higher anti-CMV neutralization capacity of CMVIG per gram of IgG vs. standard IVIG suggests that standard IVIGs are not equivalent to or interchangeable with CMVIG.
Asunto(s)
Anticuerpos Antivirales/análisis , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G/análisis , Inmunoglobulinas Intravenosas/inmunología , Inmunoglobulinas/inmunología , Anticuerpos Antivirales/inmunología , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/virología , Humanos , Inmunoglobulinas/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéuticoRESUMEN
Outpatient parenteral antimicrobial therapy (OPAT) services are not well developed in the Republic of Ireland. A national programme is being instituted to standardise care. This survey aims to assess the current use of outpatient intravenous antibiotics and to quantify the needs that physicians identify in the development of a national programme. General medical consultant physicians and clinical microbiology consultants were contacted through the Royal College of Physicians of Ireland (RCPI) from April to June 2012. Data were analysed using SPSS version 20. A total of 512 physicians were contacted, of which 55 (10.7 %) responded. The majority, 38/55 (69 %), practice general internal medicine in combination with a medical specialty, 2 (4 %) general internal medicine alone, 8 (15 %) clinical microbiology and 7 (13 %) a medical specialty alone. Of those practising a medical specialty, 12 (27 %) practice infectious diseases. Seventy-four percent reported having discharged patients with intravenous antibiotics; however, 47 % did not have a designated service available. Of those with no service, 100 % identified a need for these resources. Of those responsible for an OPAT service, 56 % had not audited their service. The most common indications were skin and soft tissue infections, osteomyelitis and respiratory tract infection. Flucloxacillin was the most commonly reported antibiotic. Eleven percent responded that they never monitor laboratory studies for patients discharged with intravenous antibiotics. While OPAT services in Ireland are not well developed, patients are being discharged with intravenous antibiotics. This survey underscores the need to develop the national programme to standardise care and ensure patients receive safe and efficient therapy.
Asunto(s)
Atención Ambulatoria/métodos , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infusiones Parenterales/métodos , Humanos , Entrevistas como Asunto , IrlandaAsunto(s)
Infecciones Bacterianas/etiología , Enterococcus/aislamiento & purificación , Trasplante de Órganos/efectos adversos , Resistencia a la Vancomicina , Antibacterianos/uso terapéutico , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/terapia , Humanos , Factores de RiesgoRESUMEN
We evaluated the activity of CB-183,315 against Clostridium difficile, including strains that are resistant to fluoroquinolones and metronidazole and with elevated MICs to vancomycin as well as other Gram-positive intestinal pathogens. The MICs of CB-183,315 against all C. difficile isolates were ≤ 1 µg/ml. CB-183,315 had greater activity than vancomycin and metronidazole against C. difficile isolates and was more active than the comparators against vancomycin-resistant enterococcus (VRE). CB-183,315 also had excellent activity against methicillin-resistant Staphylococcus aureus (MRSA), other Clostridium spp., and Peptostreptococcus spp.
Asunto(s)
Antibacterianos/farmacología , Clostridioides difficile/efectos de los fármacos , Intestinos/microbiología , Lipopéptidos/farmacología , Vancomicina/farmacología , Clostridioides difficile/patogenicidad , Farmacorresistencia Bacteriana Múltiple , Enterococcus/efectos de los fármacos , Enterococcus/patogenicidad , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Metronidazol/farmacología , Pruebas de Sensibilidad Microbiana , Peptostreptococcus/efectos de los fármacos , Peptostreptococcus/patogenicidadRESUMEN
The susceptibility trends for the species of the Bacteroides fragilis group against various antibiotics were determined using data from 4 years [2006-2009] on 1957 isolates referred by 8 medical centers participating in a National Survey for the Susceptibility of B. fragilis. The antibiotic test panel included doripenem, ertapenem, imipenem, meropenem, ampicillin:sulbactam, piperacillin:tazobactam, cefoxitin, clindamycin, moxifloxacin, tigecycline, chloramphenicol and metronidazole. MICs were determined using agar dilution methods following CLSI recommendations. Genetic analysis of isolates from 2008 with elevated MICs (>2 µg/mL) to one or more of the carbapenems to detect presence of the cfiA gene was performed using PCR methodology. The results showed an increase in the resistance rates to the ß-lactam antibiotics. High resistance rates were seen for clindamycin and moxifloxacin (as high as 60% for clindamycin and >80% for moxifloxacin), with relatively stable low resistance (5.4%) for tigecycline. For carbapenems, resistance in B. fragilis was 1.1%-2.5% in 2008-9. One isolate resistant to metronidazole (MIC 32 µg/mL) was observed as well as isolates with elevated MICs to chloramphenicol (16 µg/mL). Genetic analysis indicated that the cfiA gene was present in some but not all of the isolates with high MICs to the carbapenems. These data indicate that there continue to be changes in susceptibility over time, and that resistance can be seen among the carbapenems. High antibiotic resistance rates tend to be associated with specific species.
Asunto(s)
Bacteroides fragilis/efectos de los fármacos , Bacteroides fragilis/genética , Carbapenémicos/farmacología , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Bacteroides fragilis/aislamiento & purificación , Farmacorresistencia Microbiana , Genes Bacterianos , Humanos , Pruebas de Sensibilidad Microbiana/métodos , beta-Lactamasas/genéticaRESUMEN
BACKGROUND/OBJECTIVES: Live-attenuated influenza vaccine (LAIV) protects against influenza by mucosal activation of the immune system. Studies in animals and adults have demonstrated that probiotics improve the immune response to mucosally delivered vaccines. We hypothesized that Lactobacillus GG (LGG) would function as an immune adjuvant to increase rates of seroconversion after LAIV administration. SUBJECTS/METHODS: We conducted a randomized double-blind placebo-controlled pilot study to determine whether LGG improved rates of seroconversion after administration of LAIV. We studied 42 healthy adults during the 2007-2008 influenza season. All subjects received LAIV and then were randomized to LGG or placebo, twice daily for 28 days. Hemagglutinin inhibition titers were assessed at baseline, at day 28 and at day 56 to determine the rates of seroconversion. Subjects were assessed for adverse events throughout the study period. RESULTS: A total of 39 subjects completed the per-protocol analysis. Both LGG and LAIV were well tolerated. Protection rates against the vaccine H1N1 and B strains were suboptimal in subjects receiving LGG and placebo. For the H3N2 strain, 84% receiving LGG vs 55% receiving placebo had a protective titer 28 days after vaccination (odds of having a protective titer was 1.84 95% confidence interval 1.04-3.22, P=0.048). CONCLUSION: Lactobacillus GG is potential as an important adjuvant to improve influenza vaccine immunogenicity. Future studies of probiotics as immune adjuvants might need to specifically consider examining vaccine-naïve or sero-negative subjects, target mucosal immune responses or focus on groups known to have poor response to influenza vaccines.
Asunto(s)
Adyuvantes Inmunológicos/metabolismo , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Lactobacillus/inmunología , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/efectos adversos , Gripe Humana/inmunología , Masculino , Proyectos Piloto , Probióticos/metabolismo , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Adulto JovenRESUMEN
Reactivation of latent VZV remains a significant cause of morbidity after SCT. Twenty-five percent or more of patients undergoing SCT will experience zoster within the first year after transplant. Short-course (<1 year) prophylaxis with acyclovir has been shown to be effective, but compliance with five times daily dosing may be problematic. We conducted a randomized, double-blind, placebo-controlled trial of valacyclovir (VACV) 1000 mg twice daily from 4 through 24 months after SCT for the prevention of VZV. Fifty-three VZV-seropositive transplant recipients (17 auto-SCT, 36 allo-SCT) were randomized at a median of 163 days after SCT. In a modified intent-to-treat analysis of 49 patients who took study drug, 0 of 22 in the VACV arm experienced zoster reactivation, compared with 6 of 26 (23%) in the placebo arm (P=0.025). Thirty-two subjects completed therapy through the second year post transplant or first episode of zoster. Adverse events resulting in discontinuation were more frequent in the placebo group (5 of 26 vs 3 of 27 for placebo and study drug, respectively). VACV at a dose of 1000 mg twice daily through 24 months after transplant is well tolerated and effective in suppressing shingles after SCT.
Asunto(s)
Aciclovir/análogos & derivados , Antivirales/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Zóster/prevención & control , Valina/análogos & derivados , Aciclovir/efectos adversos , Aciclovir/uso terapéutico , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Factores de Tiempo , Valaciclovir , Valina/efectos adversos , Valina/uso terapéuticoRESUMEN
Blood stream infection (BSI) and acute GVHD (aGVHD) are serious complications of hematopoietic SCT (HSCT). We hypothesized that the two events were not independent of one another. We studied (1) associations between BSI and aGVHD; and (2) the impact of BSI and/or aGVHD on death within 100 days after HSCT, using a retrospective cohort analysis. Risk factor analysis was carried out using multivariable Cox proportional hazards analyses. Of 211 patients who underwent allogeneic HSCT from January 2000 to December 2005 (58% of whom underwent reduced intensity transplantation), 82 (39%) developed BSI. In 49 patients (23%), grade (gr) 2-4 aGVHD occurred. Early BSI was independently associated with an increased occurrence of subsequent aGVHD gr 2-4. CMV seropositivity was independently associated with decreased occurrence of aGVHD. aGVHD gr 2-4 independently predicted subsequent first BSI. Both BSI and aGVHD gr 2-4 were significant independent predictors of death within 100 days after HSCT. There is a strong, independent association between BSI and aGVHD. Potential explanations include the elaboration of cytokines during BSI favoring the development of aGVHD and/or the immunosuppressive treatment of aGVHD favoring the development of BSI. Future studies should be directed at the mechanistic investigations of this association.
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Bacteriemia/etiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Aguda , Adulto , Estudios de Cohortes , Infecciones por Citomegalovirus/etiología , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios RetrospectivosAsunto(s)
Infecciones por Citomegalovirus/etiología , Trasplante de Órganos/efectos adversos , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/prevención & control , Humanos , Factores de RiesgoRESUMEN
Many clinical laboratories use enzyme immunoassays (EIA) to diagnose Clostridium difficile-associated disease (CDAD). Clinicians frequently order three EIAs to "rule out" CDAD. We performed a retrospective cohort study to determine the clinical utility of repeating EIA testing to diagnose CDAD. We reviewed all EIAs performed by our laboratory during 2005, determined the total number of tests per patient and per testing episode, and calculated the relative negative predictive value (NPV) of one EIA compared to > or =2 EIAs. The laboratory performed 2,938 EIAs, of which 253 (8.6%) tests were positive. Most patients (85%) were diagnosed by the first EIA performed. Of >1,000 testing episodes that included > or =2 EIAs within 7 days, only 15 patients had a positive second or third test after negative initial testing. The relative NPV of the first EIA was 97.4%. These data suggest that using newer generation EIAs, repeated testing is of limited benefit in diagnosing CDAD.
Asunto(s)
Clostridioides difficile/aislamiento & purificación , Enterocolitis Seudomembranosa/diagnóstico , Técnicas para Inmunoenzimas/métodos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
Blood stream infection (BSI) is a serious complication of hematopoietic stem cell transplantation (HSCT). The aim of this retrospective cohort analysis was to describe BSI after HSCT, and to assess the predictors and outcomes of BSI after HSCT using multivariable modeling. Of the 243 subjects transplanted, 56% received allogeneic HSCT and 106 (43.6%) developed BSI. Of the 185 isolates, 68% were Gram-positive cocci, 21% were Gram-negative bacilli (GNR) and 11% were fungi. Type of allogeneic HSCT was an independent risk factor for BSI (hazard ratio (HR) 3.26, 95% confidence interval (CI) 1.50, 7.07, P = 0.01), as was the degree of HLA matching (HR 1.84, 95% CI 1.00, 3.37, P = 0.05). BSI was a significant independent predictor of mortality after HSCT (HR 1.79, 95% CI 1.18, 2.73, P = 0.007), after adjusting for acute graft-versus-host disease (GVHD) and allogeneic HSCT (both predicting death < or = 3 months after HSCT). In contrast to the effects of acute GVHD and allogeneic HSCT, the effect of BSI was evident throughout the post-HSCT period. GNR BSI and vancomycin-resistant enterococcal BSI also were significantly associated with death. We concluded that BSI is a common complication of HSCT associated with increased mortality throughout the post-HSCT period.