News Author: Karla Gale, MS
CME Author: Penny Murata, MD
Authors and Disclosures
CME Released: 04/09/2010; Valid for credit through 04/09/2011
April 9, 2010 — Antibiotics don't improve outcomes after incision and drainage of uncomplicated skin abscesses, new research indicates. They might prevent new abscesses at one month, however.
"We're seeing so many abscesses now," lead researcher Dr. Gillian R. Schmitz told Reuters Health. Before methicillin-resistant Staphylococcus aureus (MRSA) became so widespread, most abscess patients had diabetes or were immunocompromised, she said, "but now they're popping up all over the place in people with no traditional risk factors."
"But no one has studied best practice for treating abscesses," Dr. Schmitz added.
In a multicenter trial, she and her colleagues randomized 212 adults to receive trimethoprim-sulfamethoxazole (160 mg/800 mg) or placebo after incision and drainage of community-acquired abscesses. They instructed patients to take 2 pills twice daily for seven days. The primary outcome was treatment failure at 7 days, defined as no improvement after 2 days, development of a new separate abscess within 7 days, or worsening infection within 7 days requiring intervention.
Eighty-eight patients in the antibiotic group and 102 in the placebo group completed 7 days of follow-up; 46 and 50, respectively, returned at 30 days.
According to their March 29th online report in the Annals of Emergency Medicine, all bacterial isolates were uniformly sensitive to trimethoprim-sulfamethoxazole. Still, there was no significant difference in treatment failure rates at 7 days (17% in the antibiotic group and 26% in the placebo group, p = 0.12).
"Antibiotics don't help with resolution of infection," Dr. Schmitz said. "The most important thing is to open the wound, clean it, and get the pus out."
However, the total number of new lesions at 30 days was significantly lower in the antibiotic group: 9% vs 28% (p = 0.02).
"More study needs to be done to draw a conclusion about recurrence, because we lost so many to follow-up at 30 days," Dr. Schmitz said.
A separate trial in children with community-acquired skin abscesses found similar results. In a paper scheduled for print publication in the May issue of same journal, Dr. Myto Duong, currently at Southern Illinois University, Springfield, and associates report outcomes in 149 children after incision and drainage. The 73 children randomized to the intervention group took trimethoprim-sulfamethoxazole for 10 days (10-12 mg trimethoprim/kg/day in 2 divided doses, with a maximum of 160 mg per dose, in a liquid formulation containing 200 mg sulfamethoxazole/40 mg trimethoprim per 5 mL). The other 76 children received placebo.
The authors found no significant difference in failure rates at 10 days — 4.1% in the antibiotic group vs 5.3% in the placebo group. In addition, the antibiotic group had a significantly lower incidence of new lesions at day 10 (12.9%, vs 26.4% in the placebo group).
At 30 days, however, with 46 children in the antibiotics group and 52 in the placebo group evaluable, there was no longer a significant difference in the rate of new lesions (28.3% vs 28.8%, respectively).
"Antibiotics are not required for pediatric skin abscess resolution," Dr. Duong's group concludes, adding that further research is needed to see if antibiotics help prevent new lesions in the short term.
Both studies were limited by attrition of patients and by inclusion of subjects who were otherwise healthy, so the results can't be generalized to patients with comorbidities. In Dr. Duong's trial, medication compliance was only 66%.
In an editorial, Dr. David A. Talan of Olive View--UCLA Medical Center in Sylmar, California, states, "Antibiotics for drained simple abscesses are not required to meet the standard of care."
He told Reuters Health, "The rate of resolution of patient groups described in these studies is very high, so doctors can feel that the odds are on their side" if they forego antibiotic treatment, "and they can reassure patients there's a good chance that things will work out fine."
But, he continued, physicians should be aware of the tendency for abscesses to return, and they should advise patients to seek attention if new symptoms appear after first infection resolves.
Ann Emerg Med. Published online March 29, 2010.
Reuters Health Information 2010. © 2010 Reuters Ltd.
Clinical Context
In the November 2007 issue of Antimicrobial Agents and Chemotherapy, Rajendran and colleagues reported that after incision and drainage for abscess, improvement at 7 days occurred in 84% of patients receiving antibiotics and 91% of patients receiving placebo. In children with skin abscesses, rates of treatment failure were similar for those treated with trimethoprim-sulfamethoxazole vs placebo, as found by Duong and colleagues in the May 5, 2009, online issue of the Annals of Emergency Medicine.
This multicenter, double-blind, randomized, placebo-controlled trial evaluates whether treatment with trimethoprim-sulfamethoxazole for uncomplicated skin abscesses reduces treatment failure in the first 7 days and the rate of new lesion formation in the first 30 days after incision and drainage in adults.
Study Highlights
• 212 adults 16 years or older from a convenience sample of 220 adults with uncomplicated skin abscesses requiring incision and drainage were enrolled.
• 4 military emergency departments participated.
• Exclusion criteria were immunocompromised status, pregnancy, breast-feeding, allergy to sulfa drugs, fever or systemic illness, antibiotic use in the prior week, hospitalization in the prior month, abscess on the face, suspected tracts or fistulas, and need for drainage in the operating room.
• Standard practice was used to drain and pack abscesses.
• Incision length, irrigation, and ultrasonography use were dependent on the individual physician.
• Wound cultures were sent for aerobic and anaerobic cultures and antimicrobial susceptibility testing.
• 96 patients were randomly assigned to receive trimethoprim-sulfamethoxazole (160 mg/800 mg) 2 pills twice daily for 7 days.
• 116 patients were randomly assigned to receive placebo.
• The placebo group vs the trimethoprim-sulfamethoxazole group had similar baseline characteristics of age (range, 17 - 79 years), sex, abscess location, cellulitis size, and abscess size.
• The most common abscess location was an extremity (47% - 49%).
• Patients were asked to follow up in the emergency department at 2 days and again at 7 days for wound check.
• Primary outcome measure was treatment failure within 7 days.
• Treatment failure in 7 days was defined as no improvement after 2 days, new separate lesion within 7 days, or worsening infection within 7 days requiring intervention (increased diameter of abscess, cellulitis, fever, or systemic response requiring further antibiotic use, additional incision and drainage, surgical debridement, or hospital admission).
• Secondary outcome measure was formation of new lesions, abscess, or pustule within 30 days.
• 3 sites assessed secondary outcome by telephone calls, return visits to the emergency department, and review of medical records.
• Culture results revealed MRSA in 53% of patients overall: 47 (47%) of 100 patients in the placebo group and 50 (60%) of 84 patients in the trimethoprim-sulfamethoxazole group.
• All MRSA isolates were sensitive to trimethoprim-sulfamethoxazole.
• At 7-day follow-up of 190 (90%) of 212 subjects, the treatment failure rate was statistically similar for the placebo group (27 [26%] of 102 patients) vs the trimethoprim-sulfamethoxazole group (15 [17%] of 88 patients). The difference was 9% (P = .12).
• At 30-day follow-up of 96 (69%) of 139 subjects, new lesion formation was greater in the placebo group (14 [28%] of 50 patients) vs the trimethoprim-sulfamethoxazole group (4 [9%] of 46 patients). The difference was 19% (P = .02).
• Adverse effects were reported by 10 patients in the trimethoprim-sulfamethoxazole group: 4 had nausea, 3 were drowsy or dizzy, 1 had headache and night sweats, 1 had vaginal yeast infection, and 1 had mild allergic reaction.
• 1 patient in the placebo group reported an adverse effect of drowsiness.
• Limitations of the study were loss to follow-up, convenience sample, inability to generalize to children or to persons with compromised immune systems, and lack of standardization of incision-and-drainage technique.
Clinical Implications
• In adults with uncomplicated skin abscesses, trimethoprim-sulfamethoxazole does not decrease treatment failure at 7 days after incision and drainage.
• In adults with uncomplicated skin abscesses, trimethoprim-sulfamethoxazole might decrease the formation of new lesions at 30 days after incision and drainage
lunes, 5 de julio de 2010
Desvelan como las bacterias controlan su desplazamiento en enjambre
Una investigación, liderada por investigadores de la Universidad Autónoma de Barcelona (UAB), ha descrito uno de los mecanismos por el cual las poblaciones de bacterias patógenas controlan su dispersión por la superficie de los órganos que infectan, deteniéndose ante la presencia de un antibiótico y retomando su actividad cuando este disminuye. El proceso tiene como protagonista a la proteína recargo, que aumenta significativamente su concentración cuando se pone en marcha el mecanismo de reparación del material genético de las bacterias, desencadenado por los antibióticos. La investigación ha sido publicada en Infection and Immunity.
Para desarrollar su proceso infeccioso, muchos patógenos bacterianos se desplazan colectivamente por encima de la superficie del órgano que infectan, facilitando su colonización masiva, con la consiguiente producción de toxinas y sustancias que lesionan los tejidos del huésped. Este desplazamiento se llama movimiento en enjambre, - "swarming" en inglés-, y es similar al de los enjambres de abejas y otros animales. Algunos datos sobre el proceso molecular asociado a este desplazamiento ya habían sido descritos, pero no se conocían los mecanismos que controlaban su activación o inhibición.
En el trabajo publicado se desvela por primera vez la relación entre el mecanismo de reparación del material genético de las bacterias, llamado respuesta SOS, y el movimiento en enjambre. Los investigadores han comprobado que la presencia del antibiótico activa la respuesta SOS, aumentando la concentración de la proteína recargo. Esta proteína interfiere en la acción de la proteína Chew, implicada en el movimiento en enjambre y, como consecuencia, se detiene el movimiento poblacional. Cuando la concentración del antibiótico disminuye, la cantidad de la proteína recargo se reduce y Chew tiene de nuevo el camino libre para seguir promoviendo la dispersión de la población bacteriana.
Afectación al exterior del enjambre
Los resultados obtenidos indican que, dadas las características especiales de este tipo de movimiento colectivo, los antibióticos sólo afectarían las células del exterior del enjambre, que actuarían como sensores de la presencia del antibiótico, activando el mecanismo molecular mencionado anteriormente y evitando, así, el efecto del fármaco sobre el resto de la población bacteriana.
Los investigadores del Departamento de Genética y de Microbiología de la UAB, Jordi Barbé, Laura Medina Ruiz y Susana Campoy, que han encabezado la investigación, destacan la importancia de este descubrimiento básico, ya que puede permitir diseñar dianas que bloqueen la acción de recargo y aumentar la sensibilidad de las bacterias a los antibióticos.
La investigación se ha llevado a cabo en Salmonella enterica, miembro de un grupo bacteriano al que pertenecen numerosas especies patógenas que causan enfermedades de los sistemas digestivo y respiratorio, así como sepsis e infecciones sistémicas.
En colaboración con los investigadores de la UAB, han participado los investigadores Cristina Latasa, del Instituto de Agrobiotecnología-Universidad Pública de Navarra-CSIC-Gobierno de Navarra-y Paula Cárdenas y Juan Carlos Alonso, del Centro Nacional de Biotecnología del CSIC.
Infection and Immunity (July 2010), p. , Vol. 78, No. 7
Estudio muestra que palomas son fuente de bacterias dañinas
22 de junio de 2010, 12:37 PM
Por Kate Kelland
LONDRES (Reuters) - Un equipo de científicos identificó que las palomas, que dominan las plazas de las ciudades de todo el mundo y gozan de mala fama, transportan dos bacterias causantes de enfermedades, lo que las convierte en una amenaza para la salud pública.
Los resultados del estudio en España mostraron que pese a que estos microorganismos pueden ser dañinos para los humanos, aparentemente no causan problemas a las aves. Por lo tanto las palomas, que a menudo son llamadas "ratas con alas", pueden actuar como fuentes de peligrosas bacterias.
"Los animales que viven en contacto cercano con los humanos pueden ser riesgosas reservas de patógenos humanos", escribió Fernando Esperon, del Centro de Investigación de Salud Animal en Madrid, que lideró el estudio.
Las personas que habitan de Londres a Venecia y de Nueva York a San Francisco tienden a tener una relación de amor y odio con los millones de palomas urbanas que dominan las plazas, bares y monumentos de sus ciudades.
Sus desechos cubren la Plaza Trafalgar, en Londres; la Plaza San Marcos, en Venecia, y Times Square, en Nueva York, donde picotean sin cesar las migas que quedan de la comida.
Para este estudio, que fue publicado en la revista BioMed Central del Acta Veterinaria Scandinavica, Esperon y su equipo analizaron 118 palomas de áreas urbanas de la capital española para detectar la prevalencia de ciertas bacterias conocidas como portadoras de enfermedades en los humanos.
Los investigadores hallaron una bacteria llamada Chlamydophila psittaci en el 52,6 por ciento de las aves capturadas, y otra llamada Campylobacter jejuni en el 69,1 por ciento.
En los humanos, la psitacosis a menudo comienza con síntomas gripales y se puede convertir en una neumonía peligrosa para la vida. Y, de acuerdo a Esperon, la bacteria de la especie campylobacter es una de las principales causas de diarrea aguda en todo el mundo.
"De hecho, en muchos países, como Inglaterra y Gales, Canadá, Australia y Nueva Zelanda, la infección de Campylobacter jejuni provoca más casos de diarrea aguda que la infección con las especies de salmonella", escribió.
Al igual que otras bacterias, la salmonella también puede causar fiebre, diarrea, náuseas y vómitos.
Los científicos dijeron que, aunque las mismas aves parecían no enfermarse con las bacterias, podrían potencialmente transmitirlas a los humanos.
"Estos datos deberían tenerse en cuenta para controlar a la población de palomas", escribió el equipo.
miércoles, 16 de junio de 2010
Venta de antibióticos sólo bajo prescripción médica - México
Las autoridades prometen que, ahora sí, harán cumplir lo que la ley establece desde hace años: obligar a las farmacias a vender medicamentos sólo bajo prescripción médica. Los especialistas no auguran éxito a una medida planteada de forma aislada.
Esta vez la lucha que los altos funcionarios de salubridad darán no es para enfrentar un virus de oscuro origen, sino contra los hábitos arraigados en la población que tienen que ver con el libre consumo de medicamentos. La idea es evitar que las bacterias sigan volviéndose resistentes a los antibióticos, debido al uso abusivo de éstos.
Para lograrlo, la prescripción es tan simple que despierta el escepticismo de especialistas: las farmacias ya no deben vender, salvo contadas excepciones, antibióticos sin receta; algo que la Ley General de Salud ordena desde hace años.
Dado que las herramientas de supervisión necesarias y una campaña paralela de sensibilización sobre su importancia brillan por su ausencia, la medida parece una aspirina administrada a un paciente que requiere cirugía mayor. Al conseguir que la ley se acate, México formaría parte de un reducido grupo de países latinoamericanos que ya restringen la venta de antibióticos, integrado por Chile, Costa Rica, Perú y Venezuela.
Pero lograrlo no será fácil: las oficinas estatales de la Comisión Federal de Protección contra Riesgos Sanitarios (Cofepris) no se dan abasto para supervisar a las más de 20,000 farmacias del país.
Las consecuencias de este enorme desafío en términos de supervisión son evidentes. Si bien a partir de abril su venta quedaría restringida, esto no ha sucedido. En el país el mercado de antibióticos vale cerca de 1,000 millones de dólares anuales y estos medicamentos representan el segundo lugar de sus ventas.
Sin embargo, las autoridades tienen motivos para limitar su uso: sin indicación médica estos fármacos contribuyen a que las bacterias resistan la acción de los antibióticos. Los cálculos varían respecto a cuántos de estos fármacos se venden sin prescripción médica. El Instituto Nacional de Salud Pública (INSP) calcula que 40%.
Pero el problema de salud pública que representa la resistencia microbiana y sus causas son mucho más complejos que las cifras de la venta libre de antibióticos. De acuerdo con el INSP, alrededor de 70% de los pacientes con infecciones respiratorias y diarreicas agudas reciben recetas de antibióticos, cuando su uso se justifica sólo entre 10% y 15% de los casos.
La promoción del uso racional de medicamentos por parte de la Organización Mundial de la Salud data de los 80. Basada en la experiencia internacional, "una medida aislada está condenada al fracaso", dice Anahí Dreser, investigadora del INSP y especialista en políticas de medicamentos.
Más info en el sitio web de Instituto Nacional de Salud Pública de México
--
ReAct Latinoamérica
Sitio web: www.reactgroup.org
Email: reactlatin@ucuenca.edu.ec
Facultad de Ciencias Médicas
Universidad de Cuenca
Cuenca - Ecuador
lunes, 14 de junio de 2010
Una bacteria que nos hace inteligentes?
26 de mayo de 2010, 04:10 PM
Los animales que tuvieron contacto con la bacteria Mycobacterium vaccae mejoraron su capacidad para aprender nuevas tareas y mejoraron su estado de ánimo, afirmaron científicos estadounidenses.
Esta bacteria es terrestre y "es probable que la gente la ingiera o respire cuando pasa algún tiempo conviviendo con la naturaleza”, afirma la doctora Dorothy Matthews, profesora de The Sage Colleges en Troy, Nueva York, quien dirigió el estudio.
EXPERIMENTOS
Según información de BBC Mundo, la bacteria M. vaccae logra estimular el crecimiento de algunas neuronas provocando una mejora en los niveles de serotonina y una reducción de la ansiedad. La serotonina podría tener un papel en el aprendizaje y por consiguiente, mejoras en la inteligencia.
Los científicos decidieron realizar experimentos con ratones para comprobar estas hipótesis. El primero consistía en separar dos grupos de ratones, uno había ingerido la bacteria viva y el otro no. Luego los hacían pasar por el laberinto. “Encontramos que los ratones alimentados con M. vaccae viva navegaron por el laberinto dos veces más rápido y con menos ansiedad que los ratones del otro grupo”, dice la investigadora.
En el segundo experimento, se retiró la bacteria de su dieta. Cuando pasaron por el laberinto, se desenvolvieron de forma más lenta que cuando la habían ingerido, pero mucho más rápido que el grupo de ratones que no habían tenido contacto con el microbio.
EN CONVIVENCIA CON LAS BACTERIAS
“Los humanos somos un “hotel microbiano” ya que contamos con unos 10 microbios por cada célula que tenemos en nuestro cuerpo, o sea compartimos nuestro organismo con trillones de microbios”, dice la científica.
La investigadora cree que aunque el nuevo estudio fue llevado a cabo en ratones, podría especularse que pasar tiempo en el exterior donde está presente la M. vaccae podría tener también un impacto positivo en humanos.
“Así que el mensaje para la gente es salga al exterior, interactúe con la tierra, porque quizás esto lo podrá beneficiar de formas que nunca se imaginó”, afirma la científica.
miércoles, 12 de mayo de 2010
Proton Pump Inhibitor Use Linked to Clostridium Difficile Infection
Laurie Barclay, MD
May 11, 2010 — Use of proton pump inhibitors (PPIs) is linked to Clostridium difficile infection, according to the results of 2 studies reported in the May 10 issue of the Archives of Internal Medicine. The articles describing this prospective analysis are part of a series about PPIs in the Archives of Internal Medicine entitled "Less Is More."
First Study: Howell and Colleagues
"The incidence and severity of Clostridium difficile infections are increasing," write Michael D. Howell, MD, MPH, and colleagues from Beth Israel Deaconess Medical Center in Boston, Massachusetts. "Acid-suppressive therapy has been suggested as a risk factor for C difficile, but this remains controversial."
In this pharmacoepidemiologic cohort study, the investigators conducted a secondary analysis of prospectively collected data from 101,796 patients who were discharged from a tertiary care medical center during a 5-year period. Acid suppression treatment was the primary exposure of interest, classified by intensity (no acid suppression, histamine2-receptor antagonist [H2RA] treatment, daily PPI use, and PPI use more often than daily).
The risk for nosocomial C difficile infection increased with increasing level of acid suppression. This risk was 0.3% (95% confidence interval [CI], 0.21% - 0.31%) in patients not receiving acid suppressive treatment, 0.6% (95% CI, 0.49% - 0.79%) in those receiving H2RA treatment, 0.9% (95% CI, 0.80% - 0.98%) in those using PPIs daily, and 1.4% (95% CI, 1.15% - 1.71%) in patients using PPIs more often than daily.
The association persisted after adjustment for comorbid conditions, age, antibiotics, and propensity score–based likelihood of receiving no acid suppression treatment. The odds ratio was 1 for no acid suppression (reference), 1.53 for H2RA treatment (95% CI, 1.12 - 2.10), 1.74 for daily PPI use (95% CI, 1.39 - 2.18), and 2.36 for more frequent PPI use (95% CI, 1.79 - 3.11). A matched cohort analysis and nested case-control techniques resulted in similar estimates.
"Increasing levels of pharmacologic acid suppression are associated with increased risks of nosocomial C difficile infection," the study authors write. "This evidence of a dose-response effect provides further support for the potentially causal nature of iatrogenic acid suppression in the development of nosocomial C difficile infection."
Limitations of this study include observational design, possible residual confounding or selection bias, and lack of data about use of acid suppressive medications or antibiotics before admission.
Second Study: Linsky and Colleagues
The second study, by Amy Linsky, MD, from Boston Medical Center in Massachusetts, and colleagues, was a retrospective cohort study using administrative databases of the New England Veterans Healthcare System. From October 1, 2003, through September 30, 2008, there were 1166 inpatients and outpatients treated with metronidazole or vancomycin hydrochloride for incident C difficile infection.
Of these patients, 527 (45.2%) were given oral PPIs within 14 days of diagnosis, and 639 (54.8%) were not. The investigators measured the hazard ratio (HR) for recurrent C difficile infection, which was defined as a positive toxin result in the 15- to 90-day period after incident C difficile infection.
Compared with patients not using PPIs, those using them were more likely to have recurrent C difficile infection (25.2% vs 18.5%), with an adjusted HR of recurrent C difficile infection of 1.42 (95% CI, 1.11 - 1.82), based on Cox proportional survival methods.
Among patients exposed to PPIs, risks for recurrent C difficile infection were highest among those older than 80 years (HR, 1.86; 95% CI, 1.15 - 3.01) and among those given antibiotics not targeting C difficile during follow-up (HR, 1.71; 95% CI, 1.11 - 1.64).
"...PPI use during incident CDI [C difficile infection] treatment was associated with a 42% increased risk of recurrence," the study authors write. "Our findings warrant further studies to examine this association and careful consideration of the indications for prescribing PPIs during treatment of CDI."
Limitations of this study include use of observational databases, possible misclassification of exposure, and potential misclassifications of a positive test result for C difficile toxin alone as a clinically relevant recurrence.
Editorial: Risk Increase Not Modest
In an accompanying editorial, Mitchell H. Katz, MD, from the San Francisco Department of Public Health, San Francisco, California, describes these studies as well as the others described in the series, "Less Is More."
"The increases in the risk of Clostridium difficile infection with PPIs are not at all modest, reflecting the likely importance of gastric acid in protecting against infection from this pathogen," Dr. Katz writes.
"A pharmacoepidemiologic study of more than 1,000,000 hospital discharges in this issue of the Archives demonstrates a dose-response curve between level of acid suppression and C difficile infection.... Another article in this issue extends this association by demonstrating that the use of PPIs during treatment for C difficile infection was associated with a 42% increase in the rate of C difficile recurrence."
The authors of the study by Howell and colleagues have disclosed no relevant financial relationships. The study by Linsky and colleagues was supported by the resources of the Veterans Affairs Cooperative Studies Program and using the facilities of the Veterans Affairs Boston Healthcare System. The authors of the study by Linsky and colleagues have disclosed no relevant financial relationships.
Dr. Katz is an independent consultant for Health Management Associates.
Arch Intern Med. 2010;170:747-748, 772-778, 784
May 11, 2010 — Use of proton pump inhibitors (PPIs) is linked to Clostridium difficile infection, according to the results of 2 studies reported in the May 10 issue of the Archives of Internal Medicine. The articles describing this prospective analysis are part of a series about PPIs in the Archives of Internal Medicine entitled "Less Is More."
First Study: Howell and Colleagues
"The incidence and severity of Clostridium difficile infections are increasing," write Michael D. Howell, MD, MPH, and colleagues from Beth Israel Deaconess Medical Center in Boston, Massachusetts. "Acid-suppressive therapy has been suggested as a risk factor for C difficile, but this remains controversial."
In this pharmacoepidemiologic cohort study, the investigators conducted a secondary analysis of prospectively collected data from 101,796 patients who were discharged from a tertiary care medical center during a 5-year period. Acid suppression treatment was the primary exposure of interest, classified by intensity (no acid suppression, histamine2-receptor antagonist [H2RA] treatment, daily PPI use, and PPI use more often than daily).
The risk for nosocomial C difficile infection increased with increasing level of acid suppression. This risk was 0.3% (95% confidence interval [CI], 0.21% - 0.31%) in patients not receiving acid suppressive treatment, 0.6% (95% CI, 0.49% - 0.79%) in those receiving H2RA treatment, 0.9% (95% CI, 0.80% - 0.98%) in those using PPIs daily, and 1.4% (95% CI, 1.15% - 1.71%) in patients using PPIs more often than daily.
The association persisted after adjustment for comorbid conditions, age, antibiotics, and propensity score–based likelihood of receiving no acid suppression treatment. The odds ratio was 1 for no acid suppression (reference), 1.53 for H2RA treatment (95% CI, 1.12 - 2.10), 1.74 for daily PPI use (95% CI, 1.39 - 2.18), and 2.36 for more frequent PPI use (95% CI, 1.79 - 3.11). A matched cohort analysis and nested case-control techniques resulted in similar estimates.
"Increasing levels of pharmacologic acid suppression are associated with increased risks of nosocomial C difficile infection," the study authors write. "This evidence of a dose-response effect provides further support for the potentially causal nature of iatrogenic acid suppression in the development of nosocomial C difficile infection."
Limitations of this study include observational design, possible residual confounding or selection bias, and lack of data about use of acid suppressive medications or antibiotics before admission.
Second Study: Linsky and Colleagues
The second study, by Amy Linsky, MD, from Boston Medical Center in Massachusetts, and colleagues, was a retrospective cohort study using administrative databases of the New England Veterans Healthcare System. From October 1, 2003, through September 30, 2008, there were 1166 inpatients and outpatients treated with metronidazole or vancomycin hydrochloride for incident C difficile infection.
Of these patients, 527 (45.2%) were given oral PPIs within 14 days of diagnosis, and 639 (54.8%) were not. The investigators measured the hazard ratio (HR) for recurrent C difficile infection, which was defined as a positive toxin result in the 15- to 90-day period after incident C difficile infection.
Compared with patients not using PPIs, those using them were more likely to have recurrent C difficile infection (25.2% vs 18.5%), with an adjusted HR of recurrent C difficile infection of 1.42 (95% CI, 1.11 - 1.82), based on Cox proportional survival methods.
Among patients exposed to PPIs, risks for recurrent C difficile infection were highest among those older than 80 years (HR, 1.86; 95% CI, 1.15 - 3.01) and among those given antibiotics not targeting C difficile during follow-up (HR, 1.71; 95% CI, 1.11 - 1.64).
"...PPI use during incident CDI [C difficile infection] treatment was associated with a 42% increased risk of recurrence," the study authors write. "Our findings warrant further studies to examine this association and careful consideration of the indications for prescribing PPIs during treatment of CDI."
Limitations of this study include use of observational databases, possible misclassification of exposure, and potential misclassifications of a positive test result for C difficile toxin alone as a clinically relevant recurrence.
Editorial: Risk Increase Not Modest
In an accompanying editorial, Mitchell H. Katz, MD, from the San Francisco Department of Public Health, San Francisco, California, describes these studies as well as the others described in the series, "Less Is More."
"The increases in the risk of Clostridium difficile infection with PPIs are not at all modest, reflecting the likely importance of gastric acid in protecting against infection from this pathogen," Dr. Katz writes.
"A pharmacoepidemiologic study of more than 1,000,000 hospital discharges in this issue of the Archives demonstrates a dose-response curve between level of acid suppression and C difficile infection.... Another article in this issue extends this association by demonstrating that the use of PPIs during treatment for C difficile infection was associated with a 42% increase in the rate of C difficile recurrence."
The authors of the study by Howell and colleagues have disclosed no relevant financial relationships. The study by Linsky and colleagues was supported by the resources of the Veterans Affairs Cooperative Studies Program and using the facilities of the Veterans Affairs Boston Healthcare System. The authors of the study by Linsky and colleagues have disclosed no relevant financial relationships.
Dr. Katz is an independent consultant for Health Management Associates.
Arch Intern Med. 2010;170:747-748, 772-778, 784
lunes, 10 de mayo de 2010
Carbapenemases: A Brief Review for Pediatric Infectious Disease Specialists
Overturf, Gary D. MD
Authors and Disclosures
Posted: 01/28/2010; Pediatr Infect Dis J. 2010;29(1):68-70. © 2010 Lippincott Williams & Wilkins
Abstract and Introduction
Introduction
Carbapenems are increasingly utilized against a variety of infections because of the emergence of bacteria producing extended spectrum beta-lactamases (ESBL) in the Enterobacteriaceae, particularly Escherichia coli, Klebsiella pneumoniae, and other enteric bacteria[1,2] Carbapenems (imipenem, meropenem, ertapenem, and doripenem) are often the drugs of last resort for ESBL producing organisms which are increasingly also resistant to quinolones, aminoglycosides, trimethoprim–sulfamethoxazole and other antibiotics, thereby meeting the definition of multiply drug resistant organisms.[3] In addition, the carbapenems are often relied upon for uniquely resistant isolates of Pseudomonas aeruginosa and Acinetobacter spp. However, the emergence and proliferation of bacteria producing carbapenemases are increasingly being seen in clinical practice, jeopardizing the effective use of carbapenems generating a whole new class of Gram negative "superbugs."
Resistance to carbapenems may not always due to the production of carbapenemases[4] Some resistance among Enterobacteriaceae are caused by the expression of AmpC type enzymes when combined with a limitation to cellular penetration via a porin loss, then carbapenem resistance can occur. In addition, other "conventional" beta-lactamases such as the SHV class of ESBLs with porin loss can also produce a phenotype of carbapenem resistance.[5] However, this discussion will focus on the emerging issue of carbapenemases in clinical isolates and the hazards they pose in laboratory detection and effective clinical treatment of infections.
Carbapenemases
Table 1 outlines the common carbapenemases produced by pathogenic bacteria. These enzymes fall into 3 of the Ambler classes of beta-lactamases, A, B, and D classes and include the Klebsiella pneumoniae carbapenemases (KPC), 4 serine carbapenemases (SME, NMC-A, IMI, and rare GES) and several metallo-beta-lactamases (IMI, VIM).[6,7] A last group of enzymes, OXA, are only weakly active against carbapenems and are largely confined to Pseudomonas and Acinetobacter species, and only rarely in Enterobacteriaceae.[8] It is unknown whether OXA carbapenemases, which are confined to bacterial chromosomes and not present on mobile elements, will emerge as significant causes of resistance in bacteria other than Acinetobacter.
KPC Carbapenemases
These agents are the most commonly occurring class A carbapenemases and yet have been found only recently.[9] Although KPC 1–8 have been described, types 1 and 2 have been subsequently been found to be identical; the rest are variants of the bla KPC genes on conjugative plasmids that often carry other resistance markers such as fluoroquinolone and aminoglycoside resistance. Interspecies transfers of these enzymes have been suggested in studies in some health care facilities. KPC enzymes when present are generally broadly active against all beta-lactams despite the fact that they may test susceptible to some carbapenems (particularly imipenem and meropenem) as well as to cefepime and cephamycins, particularly when using agar dilution methods such as disk testing and Etest.[7] Some automated systems have been associated with this difficulty as well. However, ertapenem resistance generally has been found to be the single most sensitive indicator of carbapenem resistance with KPCs, but when dilution tests are performed, the minimum inhibitory concentration (MIC) of imipenem and meropenem will be found to be elevated, to at least the "intermediate" range of MIC.
KPC enzymes have been most often in K. pneumoniae, but like ESBLs these enzymes are no longer confined to this organism, and KPCs have been found in Klebsiella oxytoca, Salmonella enterica, Citrobacter freundii, Enterobacter aerogenes, Enterobacter Cloacae, and Serratia marcescens.[7] In addition, they have been found in rare isolates of Ps. aeruginosa in Puerto Rico and Colombia. The first KPC isolates (K. pneumoniae) occurred in the United States in North Carolina and are now concentrated in New York, New Jersey, Maryland, Pennsylvania, but now rarely in Florida, Colorado, New Mexico, and California, as well as Missouri, Arkansas, Virginia, and Alabama.[7,10] However, KPCs are now widely distributed worldwide with reports in Israel, China, Greece, South America and India.[6,7]
Serine Carbapenemases
Class A serine carbapenemases are chromosomal enzymes including SME, IMI and NMC-A and plasmid borne enzymes, the GES beta-lactamases.[6,11] Imipenem and cefoxitin induce chromosomal carbapenemases; confering a unique susceptibility profile with resistance to carbapenems, penicillins, and aztreonam but susceptibility to extended spectrum cephalosporins. The activity of these enzymes is susceptible to inhibition by clavulanate, but not sulbactam. The presence of these genetic elements on chromosomes and not on mobile genetic elements, is cited as the reason that intraspecies spread has been rare. These SME group are confined in S. marcescens and the GES enzymes are also rare, but are found as cassettes within integrons on plasmids mostly in Ps. aeruginosa.
Class B Metallo-β-lactamases
Class B Metallo-β-lactamases (MBL) carbapenemases are of the Ambler class B and have a wide spectrum of activity against carbapenems, penicillins and extended spectrum cephalosporins but not aztreonam.[6,7] These enzymes require zinc as a cofactor and they are inhibited by EDTA, a chelator of divalent cations. These enzymes occur in multiple genera of Gram negative bacteria including Enterobacteriaceae as well as non-fermenters. The enzymes are found world wide and like KPCs have spread rapidly, presenting a serious threat because of the their prolific dissemination.[12] The VIM and IMP type of MBLs are the most common. The VIM MBL consist of a family of 14 enzymes, but VIM-2 predominates in most outbreaks
Laboratory Detection of Carbapenemases
Detection of carbapenemase activity in Enterobacteriaceae is a challenge particularly for the most frequent enzymes of the MBL and KPC type (Table 2). These enzymes do not always produce resistant breakpoints for carbapenems, using standardized susceptibility testing methods. Effective treatment and infection control depend upon the rapid and efficient identification of these isolates. Unfortunately, carbapenem susceptibility by reference MIC methods, such as the broth microdilution and agar dilution, are more sensitive than disk diffusion, Etest, and many automated systems.[7] However, although Enterobacteriaceae with KPC generally have higher MICs they may not test into the defined resistant range. MICs of ≥1.0 to 2.0 μ/mL against ertapenem, meropenem, or imipenem has been found to be an effective screen of the likely presence of KPCs, whereas MBLs produce MICs ≥2.0 μg/mL against imipenem or meropenem. Therefore recommendations for testing have suggested that most MBL producers will have MIC for imipenem and meropenem greater than 2.0 μg/mL and have suggested using this as a cutoff or cutoff ranging from 1 to 4 μg/mL as a "screening" dilution for possible carbapenemase production.[13] As mentioned previously still others suggest ertapenem resistance as the most sensitive screen with MICs of >1 to 2 μg/mL as the most accurate way to detect KPC and MBL carbapenemases.
Once a screen criteria, such as a resistant MIC cutoff for ertapenem or imipenem has been selected, there are a number of phenotypic tests which have been developed to detect carbapenemases in Gram negative bacteria. The Modified Hodge Test is a relatively easily performed test on a single agar plate to detect both KPC and MBL enzymes, but it cannot differentiate between them.[14] A standardized inoculum of a lawn of a reference E. coli is utilized against carbapenem disks on the isolates to be tested. Mutiple isolates can be tested on a single agar and multiple antibiotics and it relatively easy to read, but is somewhat subjective. Several versions of an EDTA disk test[7] have been used for detections for MBL carbapenemases including one which utilizes a double sided Etest with imipenem vs. imipenem with EDTA,[15] a ratio of ≥8 between the MIC of the non-EDTA enhanced versus the EDTA enhanced imipenem MIC indicates the presence of a MBL beta-lactamase.
Summary
Carbapenem resistance constitutes a serious threat to the antibiotics available to deal with increasing resistance in Gram negative pathogens infecting neonates, infants, and compromised children with nosocomial infection caused by carbapenemase and ESBL producing bacteria. The dissemination in hospitals and the location of these enzymes on highly mobile genetic elements has contributed to their rapid spread and the frequent cotransfer of multiple other antibiotic resistance factors. The ability to limit the spread of these pathogens will require effective laboratory screening methods to rapidly identify patients infected with these organisms. Although current criteria to screen for these enzymes and methods for confirmation are useful, laboratories will need new tools, perhaps molecular techniques, to make the process rapid and accurate.
Authors and Disclosures
Posted: 01/28/2010; Pediatr Infect Dis J. 2010;29(1):68-70. © 2010 Lippincott Williams & Wilkins
Abstract and Introduction
Introduction
Carbapenems are increasingly utilized against a variety of infections because of the emergence of bacteria producing extended spectrum beta-lactamases (ESBL) in the Enterobacteriaceae, particularly Escherichia coli, Klebsiella pneumoniae, and other enteric bacteria[1,2] Carbapenems (imipenem, meropenem, ertapenem, and doripenem) are often the drugs of last resort for ESBL producing organisms which are increasingly also resistant to quinolones, aminoglycosides, trimethoprim–sulfamethoxazole and other antibiotics, thereby meeting the definition of multiply drug resistant organisms.[3] In addition, the carbapenems are often relied upon for uniquely resistant isolates of Pseudomonas aeruginosa and Acinetobacter spp. However, the emergence and proliferation of bacteria producing carbapenemases are increasingly being seen in clinical practice, jeopardizing the effective use of carbapenems generating a whole new class of Gram negative "superbugs."
Resistance to carbapenems may not always due to the production of carbapenemases[4] Some resistance among Enterobacteriaceae are caused by the expression of AmpC type enzymes when combined with a limitation to cellular penetration via a porin loss, then carbapenem resistance can occur. In addition, other "conventional" beta-lactamases such as the SHV class of ESBLs with porin loss can also produce a phenotype of carbapenem resistance.[5] However, this discussion will focus on the emerging issue of carbapenemases in clinical isolates and the hazards they pose in laboratory detection and effective clinical treatment of infections.
Carbapenemases
Table 1 outlines the common carbapenemases produced by pathogenic bacteria. These enzymes fall into 3 of the Ambler classes of beta-lactamases, A, B, and D classes and include the Klebsiella pneumoniae carbapenemases (KPC), 4 serine carbapenemases (SME, NMC-A, IMI, and rare GES) and several metallo-beta-lactamases (IMI, VIM).[6,7] A last group of enzymes, OXA, are only weakly active against carbapenems and are largely confined to Pseudomonas and Acinetobacter species, and only rarely in Enterobacteriaceae.[8] It is unknown whether OXA carbapenemases, which are confined to bacterial chromosomes and not present on mobile elements, will emerge as significant causes of resistance in bacteria other than Acinetobacter.
KPC Carbapenemases
These agents are the most commonly occurring class A carbapenemases and yet have been found only recently.[9] Although KPC 1–8 have been described, types 1 and 2 have been subsequently been found to be identical; the rest are variants of the bla KPC genes on conjugative plasmids that often carry other resistance markers such as fluoroquinolone and aminoglycoside resistance. Interspecies transfers of these enzymes have been suggested in studies in some health care facilities. KPC enzymes when present are generally broadly active against all beta-lactams despite the fact that they may test susceptible to some carbapenems (particularly imipenem and meropenem) as well as to cefepime and cephamycins, particularly when using agar dilution methods such as disk testing and Etest.[7] Some automated systems have been associated with this difficulty as well. However, ertapenem resistance generally has been found to be the single most sensitive indicator of carbapenem resistance with KPCs, but when dilution tests are performed, the minimum inhibitory concentration (MIC) of imipenem and meropenem will be found to be elevated, to at least the "intermediate" range of MIC.
KPC enzymes have been most often in K. pneumoniae, but like ESBLs these enzymes are no longer confined to this organism, and KPCs have been found in Klebsiella oxytoca, Salmonella enterica, Citrobacter freundii, Enterobacter aerogenes, Enterobacter Cloacae, and Serratia marcescens.[7] In addition, they have been found in rare isolates of Ps. aeruginosa in Puerto Rico and Colombia. The first KPC isolates (K. pneumoniae) occurred in the United States in North Carolina and are now concentrated in New York, New Jersey, Maryland, Pennsylvania, but now rarely in Florida, Colorado, New Mexico, and California, as well as Missouri, Arkansas, Virginia, and Alabama.[7,10] However, KPCs are now widely distributed worldwide with reports in Israel, China, Greece, South America and India.[6,7]
Serine Carbapenemases
Class A serine carbapenemases are chromosomal enzymes including SME, IMI and NMC-A and plasmid borne enzymes, the GES beta-lactamases.[6,11] Imipenem and cefoxitin induce chromosomal carbapenemases; confering a unique susceptibility profile with resistance to carbapenems, penicillins, and aztreonam but susceptibility to extended spectrum cephalosporins. The activity of these enzymes is susceptible to inhibition by clavulanate, but not sulbactam. The presence of these genetic elements on chromosomes and not on mobile genetic elements, is cited as the reason that intraspecies spread has been rare. These SME group are confined in S. marcescens and the GES enzymes are also rare, but are found as cassettes within integrons on plasmids mostly in Ps. aeruginosa.
Class B Metallo-β-lactamases
Class B Metallo-β-lactamases (MBL) carbapenemases are of the Ambler class B and have a wide spectrum of activity against carbapenems, penicillins and extended spectrum cephalosporins but not aztreonam.[6,7] These enzymes require zinc as a cofactor and they are inhibited by EDTA, a chelator of divalent cations. These enzymes occur in multiple genera of Gram negative bacteria including Enterobacteriaceae as well as non-fermenters. The enzymes are found world wide and like KPCs have spread rapidly, presenting a serious threat because of the their prolific dissemination.[12] The VIM and IMP type of MBLs are the most common. The VIM MBL consist of a family of 14 enzymes, but VIM-2 predominates in most outbreaks
Laboratory Detection of Carbapenemases
Detection of carbapenemase activity in Enterobacteriaceae is a challenge particularly for the most frequent enzymes of the MBL and KPC type (Table 2). These enzymes do not always produce resistant breakpoints for carbapenems, using standardized susceptibility testing methods. Effective treatment and infection control depend upon the rapid and efficient identification of these isolates. Unfortunately, carbapenem susceptibility by reference MIC methods, such as the broth microdilution and agar dilution, are more sensitive than disk diffusion, Etest, and many automated systems.[7] However, although Enterobacteriaceae with KPC generally have higher MICs they may not test into the defined resistant range. MICs of ≥1.0 to 2.0 μ/mL against ertapenem, meropenem, or imipenem has been found to be an effective screen of the likely presence of KPCs, whereas MBLs produce MICs ≥2.0 μg/mL against imipenem or meropenem. Therefore recommendations for testing have suggested that most MBL producers will have MIC for imipenem and meropenem greater than 2.0 μg/mL and have suggested using this as a cutoff or cutoff ranging from 1 to 4 μg/mL as a "screening" dilution for possible carbapenemase production.[13] As mentioned previously still others suggest ertapenem resistance as the most sensitive screen with MICs of >1 to 2 μg/mL as the most accurate way to detect KPC and MBL carbapenemases.
Once a screen criteria, such as a resistant MIC cutoff for ertapenem or imipenem has been selected, there are a number of phenotypic tests which have been developed to detect carbapenemases in Gram negative bacteria. The Modified Hodge Test is a relatively easily performed test on a single agar plate to detect both KPC and MBL enzymes, but it cannot differentiate between them.[14] A standardized inoculum of a lawn of a reference E. coli is utilized against carbapenem disks on the isolates to be tested. Mutiple isolates can be tested on a single agar and multiple antibiotics and it relatively easy to read, but is somewhat subjective. Several versions of an EDTA disk test[7] have been used for detections for MBL carbapenemases including one which utilizes a double sided Etest with imipenem vs. imipenem with EDTA,[15] a ratio of ≥8 between the MIC of the non-EDTA enhanced versus the EDTA enhanced imipenem MIC indicates the presence of a MBL beta-lactamase.
Summary
Carbapenem resistance constitutes a serious threat to the antibiotics available to deal with increasing resistance in Gram negative pathogens infecting neonates, infants, and compromised children with nosocomial infection caused by carbapenemase and ESBL producing bacteria. The dissemination in hospitals and the location of these enzymes on highly mobile genetic elements has contributed to their rapid spread and the frequent cotransfer of multiple other antibiotic resistance factors. The ability to limit the spread of these pathogens will require effective laboratory screening methods to rapidly identify patients infected with these organisms. Although current criteria to screen for these enzymes and methods for confirmation are useful, laboratories will need new tools, perhaps molecular techniques, to make the process rapid and accurate.
Suscribirse a:
Entradas (Atom)
