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1.
Clin Infect Dis ; 73(11): e4568-e4577, 2021 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-32521007

RESUMEN

BACKGROUND: A household approach to decolonization decreases skin and soft tissue infection (SSTI) incidence, though this is burdensome and costly. As prior SSTI increases risk for SSTI, we hypothesized that the effectiveness of decolonization measures to prevent SSTI when targeted to household members with prior year SSTI would be noninferior to decolonizing all household members. METHODS: Upon completion of our 12-month observational Household Observation of Methicillin-resistant Staphylococcus aureus in the Environment (HOME) study, 102 households were enrolled in HOME2, a 12-month, randomized noninferiority trial. Pediatric index patients with community-associated methicillin-resistant Staphylococcus aureus (MRSA) SSTI, their household contacts, and pets were enrolled. Households were randomized 1:1 to the personalized (decolonization performed only by household members who experienced SSTI during the HOME study) or household (decolonization performed by all household members) approaches. The 5-day regimen included hygiene education, twice-daily intranasal mupirocin, and daily bleach-water baths. At 5 follow-up visits in participants' homes, swabs to detect S. aureus were collected from participants, environmental surfaces, and pets; incident SSTIs were ascertained. RESULTS: Noninferiority of the personalized approach was established for the primary outcome 3-month cumulative SSTI: 23 of 212 (10.8%) participants reported SSTI in household approach households, while 23 of 236 (9.7%) participants reported SSTI in personalized approach households (difference in proportions, -1.1% [95% confidence interval, -6.7% to 4.5%]). In multivariable analyses, prior year SSTI and baseline MRSA colonization were associated with cumulative SSTI. CONCLUSIONS: The personalized approach was noninferior to the household approach in preventing SSTI. Future studies should interrogate longer durations of decolonization and/or decontamination of the household environment to reduce household MRSA burden. CLINICAL TRIALS REGISTRATION: NCT01814371.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones de los Tejidos Blandos , Infecciones Estafilocócicas , Infecciones Cutáneas Estafilocócicas , Antibacterianos/uso terapéutico , Niño , Humanos , Mupirocina/uso terapéutico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/prevención & control , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/prevención & control , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/prevención & control , Staphylococcus aureus
2.
N Engl J Med ; 376(26): 2545-2555, 2017 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-28657870

RESUMEN

BACKGROUND: Uncomplicated skin abscesses are common, yet the appropriate management of the condition in the era of community-associated methicillin-resistant Staphylococcus aureus (MRSA) is unclear. METHODS: We conducted a multicenter, prospective, double-blind trial involving outpatient adults and children. Patients were stratified according to the presence of a surgically drainable abscess, abscess size, the number of sites of skin infection, and the presence of nonpurulent cellulitis. Participants with a skin abscess 5 cm or smaller in diameter were enrolled. After abscess incision and drainage, participants were randomly assigned to receive clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), or placebo for 10 days. The primary outcome was clinical cure 7 to 10 days after the end of treatment. RESULTS: We enrolled 786 participants: 505 (64.2%) were adults and 281 (35.8%) were children. A total of 448 (57.0%) of the participants were male. S. aureus was isolated from 527 participants (67.0%), and MRSA was isolated from 388 (49.4%). Ten days after therapy in the intention-to-treat population, the cure rate among participants in the clindamycin group was similar to that in the TMP-SMX group (221 of 266 participants [83.1%] and 215 of 263 participants [81.7%], respectively; P=0.73), and the cure rate in each active-treatment group was higher than that in the placebo group (177 of 257 participants [68.9%], P<0.001 for both comparisons). The results in the population of patients who could be evaluated were similar. This beneficial effect was restricted to participants with S. aureus infection. Among the participants who were initially cured, new infections at 1 month of follow-up were less common in the clindamycin group (15 of 221, 6.8%) than in the TMP-SMX group (29 of 215 [13.5%], P=0.03) or the placebo group (22 of 177 [12.4%], P=0.06). Adverse events were more frequent with clindamycin (58 of 265 [21.9%]) than with TMP-SMX (29 of 261 [11.1%]) or placebo (32 of 255 [12.5%]); all adverse events resolved without sequelae. One participant who received TMP-SMX had a hypersensitivity reaction. CONCLUSIONS: As compared with incision and drainage alone, clindamycin or TMP-SMX in conjunction with incision and drainage improves short-term outcomes in patients who have a simple abscess. This benefit must be weighed against the known side-effect profile of these antimicrobials. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00730028 .).


Asunto(s)
Absceso/tratamiento farmacológico , Antibacterianos/uso terapéutico , Clindamicina/uso terapéutico , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Absceso/terapia , Adolescente , Adulto , Antibacterianos/efectos adversos , Niño , Preescolar , Clindamicina/efectos adversos , Terapia Combinada , Método Doble Ciego , Drenaje , Femenino , Humanos , Lactante , Análisis de Intención de Tratar , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Estudios Prospectivos , Enfermedades Cutáneas Bacterianas/terapia , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/aislamiento & purificación , Combinación Trimetoprim y Sulfametoxazol/efectos adversos
4.
Clin Infect Dis ; 66(2): 191-197, 2018 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-29020285

RESUMEN

Background: Staphylococcus aureus colonization poses risk for subsequent skin and soft tissue infection (SSTI). We hypothesized that including systemic antibiotics in the management of S. aureus SSTI, in conjunction with incision and drainage, would reduce S. aureus colonization and incidence of recurrent infection. Methods: We prospectively evaluated 383 children with S. aureus SSTI requiring incision and drainage and S. aureus colonization in the anterior nares, axillae, or inguinal folds at baseline screening. Systemic antibiotic prescribing at the point of care was recorded. Repeat colonization sampling was performed within 3 months (median, 38 days; interquartile range, 22-50 days) in 357 participants. Incidence of recurrent infection was ascertained for up to 1 year. Results: Participants prescribed guideline-recommended empiric antibiotics for purulent SSTI were less likely to remain colonized at follow-up sampling (adjusted hazard ratio [aHR], 0.49; 95% confidence interval [CI], .30-.79) and less likely to have recurrent SSTI (aHR, 0.57; 95% CI, .34-.94) than those not receiving guideline-recommended empiric antibiotics for their SSTI. Additionally, participants remaining colonized at repeat sampling were more likely to report a recurrent infection over 12 months (aHR, 2.37; 95% CI, 1.69-3.31). Clindamycin was more effective than trimethoprim-sulfamethoxazole (TMP-SMX) in eradicating S. aureus colonization (44% vs 57% remained colonized, P = .03) and preventing recurrent SSTI (31% vs 47% experienced recurrence, P = .008). Conclusions: Systemic antibiotics, as part of acute SSTI management, impact S. aureus colonization, contributing to a decreased incidence of recurrent SSTI. The mechanism by which clindamycin differentially affects colonization and recurrent SSTI compared to TMP-SMX warrants further study.


Asunto(s)
Antibacterianos/administración & dosificación , Portador Sano/epidemiología , Infecciones Cutáneas Estafilocócicas/epidemiología , Staphylococcus aureus/aislamiento & purificación , Adolescente , Niño , Preescolar , Drenaje , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Estudios Longitudinales , Masculino , Mucosa Nasal/microbiología , Estudios Prospectivos , Recurrencia , Piel/microbiología , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/cirugía , Herida Quirúrgica , Encuestas y Cuestionarios , Adulto Joven
5.
Pediatr Res ; 84(5): 668-676, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30135590

RESUMEN

BACKGROUND: Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs). To develop interventions to prevent recurrent infections, household attributes and individual practices influencing S. aureus colonization must be discerned. METHODS: Households of healthy children with methicillin-resistant S. aureus (MRSA) SSTI (n = 150; 671 participants) were interviewed regarding health history, activities, and hygiene practices. S. aureus colonization was assessed in household members, and recovered isolates were typed by repetitive sequence-based PCR. RESULTS: The number of unique strain types in a household (median 1, range 0-7) correlated with the number of colonized individuals (p < 0.001). The MRSA infecting strain type colonized a household member in 57% of 91 households with an available infecting strain, and was the most common strain type recovered in 45% of these households. In multivariable models, household MRSA colonization burden (p < 0.001), sharing a bedroom with MRSA-colonized individuals (p = 0.03), renting dwelling (p = 0.048), and warmer seasons (p = 0.02) were associated with increased MRSA colonization. Increasing age (p = 0.02), bathing at least daily (p = 0.01), and antibacterial soap use (p = 0.03) correlated with reduced MRSA colonization. CONCLUSIONS: This study identified practices that correlate with MRSA colonization, which will inform physician counseling and multifaceted interventions among MRSA-affected households to mitigate MRSA in the community.


Asunto(s)
Composición Familiar , Higiene , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Modelos Teóricos , Estaciones del Año , Adulto , Portador Sano , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Especificidad de la Especie
6.
Open Forum Infect Dis ; 10(11): ofad563, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38023538

RESUMEN

Background: Invasive infections caused by Streptococcus pyogenes (invasive group A streptococcus [iGAS]) and Streptococcus pneumoniae (invasive pneumococcal disease [IPD]) decreased substantially at the beginning of the COVID-19 pandemic. Our study sought to evaluate the extent of this decrease and the trends of these infections since reversion of societal adjustments incident to the pandemic. We also wanted to compare the frequency of these infections with invasive community-onset Staphylococcus aureus (I-CO-SA) infections and common respiratory viral infections in this period. Methods: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures from July 2018 through December 2022. Admission data were used to estimate frequency. For comparison, rates of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2 were estimated by the number of positive viral test results at each institution. Results: I-CO-SA infections showed little variation in the study period. Rates of iGAS infection and IPD decreased by 46% and 44%, respectively, from 2019 to 2020, coinciding with a substantial decrease in RSV and influenza. In 2022, RSV and influenza infection rates increased to prepandemic winter season rates, coinciding with a return to prepandemic rates of IPD (225% increase from 2021 to 2022) and a surge above prepandemic rates of iGAS infections (543% increase from 2021 to 2022). Conclusions: The COVID-19 pandemic had an unexpected influence on IPD and iGAS infections that was temporally related to changes in rates of viral infections.

7.
Microbiol Spectr ; 10(2): e0267221, 2022 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-35384711

RESUMEN

Decolonization with topical antimicrobials is frequently prescribed in health care and community settings to prevent Staphylococcus aureus infection. However, effects on commensal skin microbial communities remains largely unexplored. Within a household affected by recurrent methicillin-resistant S. aureus skin and soft tissue infections (SSTI), skin swabs were collected from the anterior nares, axillae, and inguinal folds of 14 participants at 1- to 3-month intervals over 24 months. Four household members experienced SSTI during the first 12-months (observational period) and were prescribed a 5-day decolonization regimen with intranasal mupirocin and bleach water baths at the 12-month study visit. We sequenced the 16S rRNA gene V1-V2 region and compared bacterial community characteristics between the pre- and post-intervention periods and between younger and older subjects. The median Shannon diversity index was stable during the 12-month observational period at all three body sites. Bacterial community characteristics (diversity, stability, and taxonomic composition) varied with age. Among all household members, not exclusively among the four performing decolonization, diversity was unstable throughout the year post-intervention. In the month after decolonization, bacterial communities were changed. Although communities largely returned to their baseline states, relative abundance of some taxa remained changed throughout the year following decolonization (e.g., more abundant Bacillus; less abundant Cutibacterium). This 5-day decolonization regimen caused disruption of skin bacteria, and effects differed in younger and older subjects. Some effects were observed throughout the year post-intervention, which emphasizes the need for better understanding of the collateral effects of decolonization for S. aureus eradication. IMPORTANCE Decolonization with topical antimicrobials is frequently prescribed to prevent Staphylococcus aureus infection, but the effects on commensal skin bacteria are undetermined. We found that decolonization with mupirocin and bleach water baths leads to sustained disruption of bacterial communities.


Asunto(s)
Antiinfecciosos Locales , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinfecciosos Locales/farmacología , Portador Sano , Clorhexidina/farmacología , Humanos , Mupirocina/farmacología , Mupirocina/uso terapéutico , ARN Ribosómico 16S , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/genética , Agua
8.
J Perinatol ; 41(6): 1285-1292, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33649431

RESUMEN

OBJECTIVE: To identify factors associated with development of symptomatic infection in infants colonized with methicillin-resistant Staphylococcus aureus (MRSA) in the Neonatal Intensive Care Unit (NICU). STUDY DESIGN: This case-control study was performed at St. Louis Children's Hospital NICU from 2009 to 2019. The MRSA-colonized infants who developed symptomatic MRSA infection (cases) were matched 1:3 with MRSA-colonized infants who did not develop infection (controls). Demographics and characteristics of NICU course were compared between groups. Longitudinal information from subsequent hospitalizations was also obtained. RESULTS: Forty-two infected cases were compared with 126 colonized-only controls. Cases became colonized earlier in their NICU stay, were less likely to have received mupirocin for decolonization, and had a longer course of mechanical ventilation than controls. Longitudinally, cases had a more protracted NICU course and were more likely to require hospital readmission. CONCLUSION: Progression from MRSA colonization to symptomatic infection is associated with increased morbidity and may be mitigated through decolonization.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Estudios de Casos y Controles , Niño , Enfermedad Crítica , Humanos , Recién Nacido
9.
Lancet Infect Dis ; 20(2): 188-198, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31784369

RESUMEN

BACKGROUND: Devising effective, targeted approaches to prevent recurrent meticillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection requires an understanding of factors driving MRSA acquisition. We comprehensively defined household longitudinal, strain-level S aureus transmission dynamics in households of children with community-associated MRSA skin and soft tissue infection. METHODS: From 2012-15, otherwise healthy paediatric patients with culture-confirmed, community-onset MRSA infections were recruited for the Household Observation of MRSA in the Environment (HOME) prospective cohort study from hospitals and community practices in metropolitan St Louis (MO, USA). Children with health-care-related risk factors were excluded, as determined by evidence of recent hospital admission, an invasive medical device, or residence in a long-term care facility. Household contacts (individuals sleeping in the home ≥four nights per week) and indoor dogs and cats were also enrolled. A baseline visit took place at the index patient's primary home, followed by four quarterly visits over 12 months. At each visit, interviews were done and serial cultures were collected, to detect S aureus from three anatomic sites of household members, two anatomic sites on dogs and cats, and 21 environmental surfaces. Molecular typing was done by repetitive-sequence PCR to define distinct S aureus strains within each household. Longitudinal, multivariable generalised mixed-effects logistic regression models identified factors associated with S aureus acquisition. FINDINGS: Across household members, pets, and environmental surfaces, 1267 strain acquisition events were observed. Acquisitions were driven equally by 510 introductions of novel strains into households and 602 transmissions within households, each associated with distinct factors. Frequent handwashing decreased the likelihood of novel strain introduction into the household (odds ratio [OR] 0·86, credible interval [CrI] 0·74-1·01). Transmission recipients were less likely to own their homes (OR 0·77, CrI 0·63-0·94) and were more likely to share bedrooms with strain-colonised individuals (OR 1·33, CrI 1·12-1·58), live in homes with higher environmental S aureus contamination burden (OR 3·97, CrI 1·96-8·20), and report interval skin and soft tissue infection (OR 1·32, CrI 1·07-1·64). Transmission sources were more likely to share bath towels (OR 1·25, CrI 1·01-1·57). Pets were often transmission recipients, but rarely the sole transmission source. INTERPRETATION: The household environment plays a key role in transmission, a factor associated with skin and soft tissue infection. Future interventions should inclusively target household members and the environment, focusing on straightforward changes in hand hygiene and household sharing behaviours. FUNDING: National Institutes of Health, Agency for Healthcare Research and Quality, Children's Discovery Institute, Burroughs Wellcome Foundation, Defense Advanced Research Projects Agency.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina/patogenicidad , Piel/microbiología , Infecciones de los Tejidos Blandos/transmisión , Infecciones Estafilocócicas/transmisión , Infecciones Cutáneas Estafilocócicas/transmisión , Animales , Enfermedades de los Gatos/microbiología , Enfermedades de los Gatos/transmisión , Gatos , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/transmisión , Enfermedades de los Perros/microbiología , Enfermedades de los Perros/transmisión , Perros , Composición Familiar , Desinfección de las Manos/métodos , Humanos , Estudios Longitudinales , Meticilina/uso terapéutico , Estudios Prospectivos , Factores de Riesgo , Infecciones de los Tejidos Blandos/microbiología , Infecciones Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/microbiología
10.
JAMA Pediatr ; 174(6): 552-562, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32227144

RESUMEN

Importance: The longitudinal association among persistent Staphylococcus aureus colonization, household environmental contamination, and recurrent skin and soft tissue infection (SSTI) is largely unexplored to date. Objectives: To identify factors associated with persistent S aureus colonization and recurrent SSTI in households with children with community-associated methicillin-resistant S aureus (MRSA) SSTI. Design, Setting, and Participants: This 12-month prospective cohort study included 150 children with community-associated MRSA SSTI, 542 household contacts, and 154 pets enrolled from January 3, 2012, through October 20, 2015. A total of 5 quarterly home visits were made to 150 households in the St Louis, Missouri, region. Statistical analysis was performed from September 18, 2018, to January 7, 2020. Exposures: Covariates used in S aureus strain persistence and interval SSTI models included S aureus colonization and contamination measures, personal hygiene and sharing habits, health history, activities external to the home, and household characteristics (eg, cleanliness, crowding, home ownership, and pets). Serial samples to detect S aureus were collected from household members at 3 anatomic sites, from pets at 2 anatomic sites, and from environmental surfaces at 21 sites. Main Outcomes and Measures: Molecular epidemiologic findings of S aureus isolates were assessed via repetitive-sequence polymerase chain reaction. Individual persistent colonization was defined as colonization by an identical strain for 2 consecutive samplings. Longitudinal, multivariable generalized mixed-effects logistic regression models were used to assess factors associated with persistent S aureus personal colonization, environmental contamination, and interval SSTI. Results: Among 692 household members in 150 households, 326 (47%) were male and 366 (53%) were female, with a median age of 14.82 years (range, 0.05-82.25 years). Of 540 participants completing all 5 samplings, 213 (39%) were persistently colonized with S aureus, most often in the nares and with the strain infecting the index patient at enrollment. Nine pets (8%) were persistently colonized with S aureus. Participants reporting interval intranasal mupirocin application were less likely to experience persistent colonization (odds ratio [OR], 0.44; 95% credible interval [CrI], 0.30-0.66), whereas increasing strain-specific environmental contamination pressure was associated with increased individual persistent colonization (OR, 1.17; 95% CrI, 1.06-1.30). Strains with higher colonization pressure (OR, 1.47; 95% CrI, 1.25-1.71) and MRSA strains (OR, 1.57; 95% CrI, 1.16-2.19) were more likely to persist. Seventy-six index patients (53%) and 101 household contacts (19%) reported interval SSTIs. Individuals persistently colonized with MRSA (OR, 1.56; 95% CrI, 1.17-2.11), those with a history of SSTI (OR, 2.55; 95% CrI, 1.88-3.47), and index patients (OR, 1.54; 95% CrI, 1.07-2.23) were more likely to report an interval SSTI. Conclusions and Relevance: The study findings suggest that recurrent SSTI is associated with persistent MRSA colonization of household members and contamination of environmental surfaces. Future studies may elucidate the effectiveness of specific combinations of personal decolonization and environmental decontamination efforts in eradicating persistent strains and mitigating recurrent SSTIs.


Asunto(s)
Infecciones Comunitarias Adquiridas/microbiología , Composición Familiar , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones de los Tejidos Blandos/microbiología , Infecciones Estafilocócicas/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Missouri , Mascotas , Estudios Prospectivos , Recurrencia , Factores de Riesgo
11.
J Infect ; 78(3): 200-207, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30503843

RESUMEN

OBJECTIVE: We sought to determine the prevalence, molecular epidemiology, and factors associated with Staphylococcus aureus environmental surface and pet colonization in households of children with community-associated methicillin-resistant S. aureus (CA-MRSA) infection. METHODS: Between 2012 and 2015, 150 children with CA-MRSA infections and their household contacts and pets were enrolled in this cross-sectional study in metropolitan Saint Louis, MO. Cultures to detect S. aureus were collected from 3 anatomic sites of household members, 2 dog/cat sites, and 21 environmental surfaces in each household. Molecular epidemiology of S. aureus isolates was determined via repetitive-sequence PCR. Generalized linear models were developed to identify factors associated with S. aureus/MRSA household contamination. RESULTS: MRSA was recovered from environmental surfaces in 69 (46%) households (median 2 surfaces [range 1-18]). The enrollment infecting strain type was the most common strain recovered from the environment in most (64%) households. In generalized linear models, factors associated with a higher proportion of MRSA-contaminated environmental surfaces were household member MRSA colonization burden, MRSA as the dominant S. aureus strain colonizing household members, more strain types per household member, index case African-American race, and renting (vs. owning) the home. Of 132 pets, 14% were colonized with MRSA. Pets whose primary caretaker was MRSA-colonized were more likely to be MRSA-colonized than pets whose primary caretaker was not MRSA-colonized (50% vs. 4%, p < 0.001). CONCLUSIONS: Household environments and pet dogs and cats serve as reservoirs of MRSA. Household member MRSA colonization burden predicts environmental MRSA contamination. Longitudinal studies will inform the directionality of household transmission.


Asunto(s)
Portador Sano/microbiología , Reservorios de Enfermedades/microbiología , Composición Familiar , Staphylococcus aureus Resistente a Meticilina/genética , Mascotas/microbiología , Infecciones Estafilocócicas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Portador Sano/epidemiología , Niño , Preescolar , Estudios Transversales , ADN Bacteriano/genética , Microbiología Ambiental , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Persona de Mediana Edad , Missouri/epidemiología , Infecciones Estafilocócicas/transmisión , Adulto Joven
12.
J Clin Oncol ; 28(8): 1373-9, 2010 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-20142593

RESUMEN

PURPOSE: No standard therapy exists for metastatic urothelial cancer (UC) that has progressed after initial chemotherapy. This trial was designed to assess the efficacy and tolerability of sunitinib in patients with advanced, previously treated UC. PATIENTS AND METHODS: In this phase II trial, 77 patients received sunitinib between September 2006 and January 2009 on one of two schedules (50 mg per day for 4 weeks on and 2 weeks off [cohort A], 37.5 mg per day continuously [cohort B]), using a Simon 2 stage design in each cohort separately. RESULTS: A partial response was seen in three of 45 patients (95% CI, 1% to 18%) in cohort A, and in one of 32 patients (95% CI, 0% to 16%) in cohort B. Clinical regression or stable disease was achieved in 33 of 77 patients (43%). Tumor regression lasted between 0.6 and 23.4 months with 29% of patients achieving response lasting longer than 3 months. The progression-free survival (2.4 v 2.3 months; P = .4) and overall survival (7.1 v 6.0 months; P = .4) were similar in both cohorts. There was one treatment-related death, and 47 patients (33 cohort A, 24 cohort B) experienced grade 3 or 4 toxicity. CONCLUSION: Sunitinib did not achieve the predetermined threshold of >or= 20% activity defined by Response Evaluation Criteria in Solid Tumors. However, antitumor responses were observed, identifying the vascular endothelial growth factor axis as a viable pathway for UC treatment. The reported clinical benefit in previously treated patients warrants further investigation in a disease for which there is no US Food and Drug Administration-approved treatment.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Indoles/uso terapéutico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Pirroles/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Indoles/efectos adversos , Indoles/farmacología , Masculino , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/secundario , Pirroles/efectos adversos , Pirroles/farmacología , Sunitinib , Análisis de Supervivencia , Urotelio/patología
13.
Cancer ; 115(22): 5193-201, 2009 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-19670454

RESUMEN

BACKGROUND: Despite definitive surgery, the survival of patients with high-risk urothelial carcinoma (UC) is poor. Adjuvant cisplatin-based chemotherapy may be beneficial, but it is restricted by the need for normal renal function (RF). Sequential administration of adjuvant chemotherapy facilitates drug delivery and improves survival in patients with breast cancer. The objective of this study was to evaluate the feasibility and survival impact of adjuvant, sequential chemotherapy in patients with high-risk UC. METHODS: Fifty patients were treated on 2 simultaneous protocols between 1997 and 2004. The patients on Protocol A (normal RF) received doxorubicin and gemcitabine (AG) followed by paclitaxel and cisplatin. The patients on Protocol B (impaired RF) received AG followed by paclitaxel plus carboplatin. Overall survival (OS) and disease-specific survival (DSS) were compared with a group of 203 contemporary control patients who had similar pathology and RF and who underwent surgery alone. RESULTS: The median follow-up of protocol patients was 6.5 years (range, 0.9-8.6 years), and 25 patients remained alive. The median follow-up of the control group was 4.7 years (0.0-9.2), and 68 patients remained alive. The median OS for patients on Protocol A was greater than that for controls who had good RF (4.6 years vs 2.5 years; P = .03). The median OS for patients on Protocol B was greater than that for controls who had impaired RF (3.4 years vs 2 years; P = .04). DSS for the protocol and matched control groups was similar (good RF: 4.6 years vs 3 years; P = .24; impaired RF: 3.4 years vs 3.3 years; P = .40). CONCLUSIONS: In this nonrandomized study, adjuvant, sequential chemotherapy for patients with high-risk UC did not improve DSS over that observed with surgery alone.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Insuficiencia Renal/cirugía , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante/efectos adversos , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal/mortalidad , Riesgo , Análisis de Supervivencia
14.
Cancer ; 113(9): 2471-7, 2008 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-18823036

RESUMEN

BACKGROUND: Neoadjuvant cisplatin-based chemotherapy improves survival in muscle-invasive urothelial cancer, with MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) considered the standard regimen. Gemcitabine plus cisplatin (GC) has similar efficacy and less toxicity than MVAC in metastatic disease, but is untested as neoadjuvant treatment. METHODS: The authors retrospectively evaluated patients with muscle-invasive urothelial carcinoma who received neoadjuvant GC before radical cystectomy between November 2000 and December 2006 at Memorial Sloan-Kettering Cancer Center. Post-therapy pathological downstaging to either residual disease at cystectomy (pT0) or no residual muscle-invasion (

Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Anciano , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/secundario , Carcinoma de Células Transicionales/cirugía , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Cistectomía , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de los Músculos/tratamiento farmacológico , Neoplasias de los Músculos/secundario , Neoplasias de los Músculos/cirugía , Invasividad Neoplásica , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Gemcitabina
15.
Cancer ; 109(3): 549-55, 2007 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-17200962

RESUMEN

BACKGROUND: Cisplatin-based therapy is standard in patients with advanced urothelial carcinoma but a large proportion are ineligible due to renal impairment. The safety and activity of a dose-dense carboplatin-based regimen in this patient population were explored. METHODS: Patients with advanced urothelial carcinoma who were ineligible for cisplatin were eligible based on at least 1 of the following: 1) serum creatinine >1.5 mg/dL; 2) creatinine clearance of >30 mL/min/1.73 m(2) and <60 mL/min/1.73 m(2); and/or 3) prior nephrectomy. Patients received treatment with doxorubicin plus gemcitabine every other week x 5 cycles followed by paclitaxel plus carboplatin weekly x 12 cycles. RESULTS: Twenty-five patients were treated. Myelosuppression was the major toxicity, with 28% of patients experiencing grade 3-4 neutropenia; there were only 2 (8%) episodes of febrile neutropenia. Grade > or = 3 nonhematologic toxicities were infrequent with the exception of grade > or = 3 thrombotic episodes in 4 (16%) patients. There were 5 complete responses and 9 partial responses for an overall response rate of 56% (95% confidence interval [CI]: 35%-76%). The median survival was 15 months (95% CI: 11-30). At a median follow-up for survivors of 45 months, 7 (28%) patients are disease-free. CONCLUSIONS: Dose-dense sequential chemotherapy is tolerable and active in patients with urothelial carcinoma and renal impairment. Prolonged disease-free survival is achievable in a subset of patients with primary unresectable disease or lymph-node only metastases treated with carboplatin-based therapy +/- surgical consolidation. Randomized trials are needed to define the optimal regimen in patients with advanced urothelial carcinoma and renal impairment.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades Renales/complicaciones , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto , Anciano , Carboplatino/administración & dosificación , Estudios de Cohortes , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/mortalidad , Gemcitabina
16.
Invest New Drugs ; 25(3): 265-70, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17146733

RESUMEN

PURPOSE: The purpose of this single-center phase II study was to determine the activity of pemetrexed administered as second-line therapy in patients with advanced urothelial carcinoma. METHODS: Patients with advanced urothelial carcinoma that had relapsed after receiving perioperative chemotherapy, or progressed on first-line chemotherapy for metastatic disease, were eligible for enrollment. Patients received pemetrexed 500 mg/m(2) every 21 days along with folic acid and vitamin B12 supplementation. RESULTS: A total of 13 patients were enrolled. An objective response was achieved in 1/12 evaluable patients for an overall response rate of 8% (90% upper limit 29%). This level of activity did not meet criteria for expansion based on the pre-defined optimal 2-stage Simon design and the trial was concluded. Treatment was generally well tolerated, however, 2/13 patients developed febrile neutropenia. Non-hematologic grade > or = 3 toxicity was rare. CONCLUSIONS: Pemetrexed as second-line therapy in advanced urothelial carcinoma is associated with modest activity. The role of this novel antifolate in chemotherapy-naïve patients warrants further investigation.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Glutamatos/uso terapéutico , Guanina/análogos & derivados , Neoplasias Pélvicas/tratamiento farmacológico , Terapia Recuperativa , Neoplasias Uretrales/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Urotelio/patología , Administración Oral , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/secundario , Esquema de Medicación , Ácido Fólico/administración & dosificación , Ácido Fólico/uso terapéutico , Glutamatos/administración & dosificación , Glutamatos/efectos adversos , Guanina/administración & dosificación , Guanina/efectos adversos , Guanina/uso terapéutico , Humanos , Infusiones Intravenosas , Neoplasias Pélvicas/mortalidad , Neoplasias Pélvicas/patología , Pemetrexed , Resultado del Tratamiento , Neoplasias Uretrales/mortalidad , Neoplasias Uretrales/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Vitamina B 12/administración & dosificación , Vitamina B 12/uso terapéutico , Complejo Vitamínico B/administración & dosificación , Complejo Vitamínico B/uso terapéutico
17.
Urology ; 69(2): 255-9, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17320659

RESUMEN

OBJECTIVES: Non-transitional cell carcinomas account for 5% to 10% of urothelial tract tumors and are each characterized by unique demographics, risk factors, and patterns of spread. A unifying feature of these malignancies is their aggressive course and poor outcome with standard chemotherapeutic regimens. Given the rarity of these tumors, no prospective data are available to guide management. METHODS: Patients with unresectable/metastatic adenocarcinoma or squamous cell, small cell, sarcomatoid, or poorly differentiated carcinoma of the urothelial tract were eligible for enrollment. Treatment consisted of paclitaxel 200 mg/m2 intravenously on day 1, cisplatin 70 mg/m2 intravenously on day 1, ifosfamide 1500 mg/m2 intravenously on days 1 to 3 plus mesna. Granulocyte colony-stimulating factor was administered with each cycle. The treatment was started again every 3 to 4 weeks for a maximum of six cycles. RESULTS: A total of 20 patients were enrolled. They had the following histologic types: adenocarcinoma in 11, squamous cell carcinoma in 8, and small cell carcinoma in 1. Patients received a median of four cycles (range one to six). The treatment was generally well tolerated, and the toxicity was predominantly hematologic. Overall, 7 (35%) of 20 patients (95% confidence interval 15% to 59%) achieved a major response (3 partial and 4 complete). The median survival for patients with adenocarcinoma was 24.8 months (95% confidence interval 10.2 to 32.3), and for those with squamous cell carcinoma it was 8.9 months (95% confidence interval 5.4 to not yet reached). CONCLUSIONS: The results of our study have shown that this regimen (ifosfamide, paclitaxel, and cisplatin) is active in patients with advanced non-transitional cell carcinoma of the urothelial tract. To our knowledge, this is the first prospective study of a chemotherapeutic regimen in this patient population.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Invasividad Neoplásica/patología , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biopsia con Aguja , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/mortalidad , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Intervalos de Confianza , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Estudios Prospectivos , Medición de Riesgo , Tasa de Supervivencia , Neoplasias Urológicas/mortalidad
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