Epidemiologic, clinical, and microbiologic description of an outbreak of Clostridium difficile associated diarrhea in Costa Rica

None; None

Abstracts

Background: Clostridium difficile associated diarrhea (CDAD) is the main cause of nosocomial diarrhea in the world.   Recently there was an outbreak of CDAD in the San Juan de Dios Hospital, San José -Costa Rica; a tertiary care center with 700 beds. This study analyses the epidemiological, clinical and microbiological characteristics of the inpatients with CDAD treated from November 2008 to June 2009.   Population and methods: A CDAD case was defined as a patient with diarrhea and with positive ELISA for C. difficile A toxin in feces. An analysis of the annual incidence of CDAD from 2004 to 2008, and the monthly incidence in 2009 at HSJD was made, as well as a retrospective and observational study of 112 medical records for patients diagnosed with CDAD treated at this hospital, from November 15, 2008 to June 15, 2009. The analysis of the data was made using descriptive statistics and measures of association.   Results: The incidence of CDAD increased significantly since the end of 2008 and reached its maximum peak in April 2009, when sanitary measures were implemented. They reduced by 75% the number of patients with CDAD in 8 months. Of the 112 medical records reviewed, 63 (56%) were men. The mean age was 65.33 years, 103 (92%) patients developed the disease while hospitalized; the mean period of hospitalization was 18.6 days. Only 9% did not suffer from any comorbidity. The most frequent comorbidities were: hypertension and type 2 diabetes, with 57.5% and 39.8%, respectively, and neuropsychiatric disease with 29.2%. A 96% (107 patients) had received three or more antibiotics before the onset of diarrhea. The mean duration of antibiotic therapy was 32 days per patient. In average, the duration of diarrhea was 10.2 days (1-90 days). Most patients were treated with metronidazole or vancomycin. The mortality directly associated to CDAD was 7%.   Discussion: An outbreak of CDAD in a national hospital with 700 beds is described. It was observed more frequently in elderly (>65 years) with long hospital stays, with multiple comorbidities and who had received multiple antibiotics for prolonged periods; mainly cefotaxime, fluoroquinolones or clindamycin. After sanitary and medical measures were implemented, the impact was reduced in 75% over 8 months

Diarrhea; Clostridium difficile; outbreak; nosocomial infection

Antecedentes: la enfermedad diarreica asociada a Clostridium difficile (EDACD) es la causa más importante de diarrea nosocomial en el mundo. En Costa Rica, se presentó recientemente un brote de EDACD en el Hospital San Juan de Dios de San José, hospital de tercer nivel con 700 camas. En el estudio se analizan las características epidemiológicas, clínicas y microbiológicas de los pacientes con EDACD atendidos entre noviembre de 2008 y junio de 2009. Pacientes y métodos: se definió como caso de EDACD un paciente con cuadro diarréico con detección de ELISA positiva por toxina A de C. difficile en heces. Se realizó un análisis de la incidencia anual desde 2004 de EDACD, y de la incidencia mensual de EDACD en 2009 en el HSJD, así como un estudio observacional y retrospectivo de 112 expedientes médicos correspondientes a pacientes con el diagnóstico de EDACD atendidos en el Hospital, en el periodo comprendido entre el 15 de noviembre de 2008 y el 15 de junio de 2009. El análisis de los datos se efectuó mediante pruebas estadísticas descriptivas y medidas de asociación. Resultados: la incidencia de EDACD aumentó desde finales de 2008, y alcanzó su pico máximo en abril de 2009, cuando se implementaron medidas sanitarias que disminuyeron en un 75% el número de pacientes en 8 meses. De los 112 expedientes médicos revisados, 63 (56%) fueron hombres. La edad promedio fue de 65,33 años; 103 (92%) pacientes desarrollaron su enfermedad mientras estuvieron hospitalizados; el tiempo promedio de internamiento fue de 18,6 días. Solo el 9% no presentó ninguna comorbilidad. Las comorbilidades más frecuentes fueron: HTA y DM tipo 2, con un 57,5% y un 39,8%, respectivamente, y enfermedad neuropsiquiátrica en un 29,2%. El 96% (107 pacientes) había recibido tres o más antibióticos antes del inicio de la diarrea. La duración promedio de la antibióticoterapia fue de 32 días por paciente. En promedio, la duración de la diarrea fue de 10,2 días (1-90 días). La mayoría de los pacientes fueron tratados con metronidazol o vancomicina. La letalidad asociada directamente a EDACD fue del 7%. Discusión: se describe un brote de EDACD en un hospital nacional de 700 camas, el cual fue observado con mayor frecuencia en adultos mayores (>65 años), con largas estancias hospitalarias, con múltiples patologías asociadas, quienes habían recibido varios antibióticos por periodos prolongados, principalmente cefotaxima, fluoroquinolonas o clindamicina. Con las medidas médico - sanitarias implementadas, se logró disminuir su incidencia en un 75%, en el transcurso de 8 mesesse describe un brote de EDACD en un hospital nacional de 700 camas, el cual fue observado con mayor frecuencia en adultos mayores (>65 años), con largas estancias hospitalarias, con múltiples patologías asociadas, quienes habían recibido varios antibióticos por periodos prolongados, principalmente cefotaxima, fluoroquinolonas o clindamicina. Con las medidas médico - sanitarias implementadas, se logró disminuir su incidencia en un 75%, en el transcurso de 8 meses

diarrea; Clostridium difficile; brote; infección nosocomial

Background: Clostridium difficile associated diarrhea (CDAD) is the main cause of nosocomial diarrhea in the world. Recently there was an outbreak of CDAD in the San Juan de Dios Hospital, San José -Costa Rica; a tertiary care center with 700 beds. This study analyses the epidemiological, clinical and microbiological characteristics of the inpatients with CDAD treated from November 2008 to June 2009. Population and methods: A CDAD case was defined as a patient with diarrhea and with positive ELISA for C. difficile A toxin in feces. An analysis of the annual incidence of CDAD from 2004 to 2008, and the monthly incidence in 2009 at HSJD was made, as well as a retrospective and observational study of 112 medical records for patients diagnosed with CDAD treated at this hospital, from November 15, 2008 to June 15, 2009. The analysis of the data was made using descriptive statistics and measures of association. Results: The incidence of CDAD increased significantly since the end of 2008 and reached its maximum peak in April 2009, when sanitary measures were implemented. They reduced by 75% the number of patients with CDAD in 8 months. Of the 112 medical records reviewed, 63 (56%) were men. The mean age was 65.33 years, 103 (92%) patients developed the disease while hospitalized; the mean period of hospitalization was 18.6 days. Only 9% did not suffer from any comorbidity. The most frequent comorbidities were: hypertension and type 2 diabetes, with 57.5% and 39.8%, respectively, and neuropsychiatric disease with 29.2%. A 96% (107 patients) had received three or more antibiotics before the onset of diarrhea. The mean duration of antibiotic therapy was 32 days per patient. In average, the duration of diarrhea was 10.2 days (1-90 days). Most patients were treated with metronidazole or vancomycin. The mortality directly associated to CDAD was 7%. Discussion: An outbreak of CDAD in a national hospital with 700 beds is described. It was observed more frequently in elderly (>65 years) with long hospital stays, with multiple comorbidities and who had received multiple antibiotics for prolonged periods; mainly cefotaxime, fluoroquinolones or clindamycin. After sanitary and medical measures were implemented, the impact was reduced in 75% over 8 months An outbreak of CDAD in a national hospital with 700 beds is described. It was observed more frequently in elderly (>65 years) with long hospital stays, with multiple comorbidities and who had received multiple antibiotics for prolonged periods; mainly cefotaxime, fluoroquinolones or clindamycin. After sanitary and medical measures were implemented, the impact was reduced in 75% over 8 months

Diarrhea; Clostridium difficile; outbreak; nosocomial infection

Clostridium difficile associated diarrhea in Costa Rica

Manuel Antonio Villalobos-Zúñiga¹, Ricardo Boza-Cordero

¹Attending Physician, Department of Infectious Diseases, San Juan de Dios Hospital. ²Attending Physician, Department of Infectious Diseases, San Juan de Dios Hospital. Associate Professor, School of Medicine, University of Costa Rica.

Correspondence:
Department of Infectious Diseases. San Juan de Dios Hospital, Caja Costarricense de Seguro Social.

Background: Clostridium difficile associated diarrhea (CDAD) is the main cause of nosocomial diarrhea in the world.

San José - Costa Rica; a tertiary care center with 700 beds. This study analyses the epidemiological, clinical and microbiological characteristics of the inpatients with CDAD treated from November 2008 to June 2009.

Population and methods: A CDAD case was defined as a patient with diarrhea and with

C. difficile A toxin in feces. An analysis of the annual incidence of CDAD from 2004 to 2008, and the monthly incidence in 2009 at HSJD was made, as well as a retrospective and observational study of 112 medical records for patients diagnosed with CDAD treated at this hospital, from November 15, 2008 to June 15, 2009. The analysis of the data was made using descriptive statistics and measures of association.

Results: The incidence of CDAD increased significantly since the end of 2008 and reached its

Discussion: An outbreak of CDAD in a national hospital with 700 beds is described. It was observed more frequently in elderly (>65 years) with long hospital stays, with multiple comorbidities and who had received multiple antibiotics for prolonged periods; mainly

Key words: Diarrhea, Clostridium difficile, outbreak, nosocomial infection.

Clostridium difficile-associated diarrhea (CDAD) is in the medical spotlight around the world, due to the constant outbreaks reported in the medical literature, with health, economic and scientific consequences.^1-3

C. difficileis an anaerobic Gram-positive bacillus, that forms spores and produces cytotoxic toxins.It is present in feces of less than 5% of the healthy adult population, and 20-30% of hospitalized patients are colonized by this bacterium during the first week.¹Due to its ability to form thermostable spores, it is not easily eradicated from the hospital environment. Despite its discovery in1935, it was not until 1977 when it was linked to a medical condition, pseudo-membranous colitis associated with the use of antibiotics, at that moment, with clindamycin.⁴

C. difficile is the most frequent cause of acquired diarrhea in the hospital, estimating tens of thousands of cases per year around the world, with costs that surpass one billion dollars.⁵In the last decades there has been observed an important rise in the number of patients, due to improved diagnostic methods, an increased use of antibiotics and chemotherapeutic agents, as well as a rise in the number of sick persons, which increases the chance of contamination by spores in health centers, with a higher probability of infection in susceptible patients.⁶

Canada between 2003 and 2005 should be noted, when several hospitals had to be shut down in order to stop the epidemic. A strain of C. difficile was identified, the one denominated hypervirulent, with some particular characteristics that were not observed before, as an increased production of A and B toxins, resistance to fluorochinolones, ability to hypersporulate and production of a binary toxin. This strain had been identified in 1982 and was denominated BI, based on the analysis of the restriction-endonuclease, but it is now known as NAP1/027 (North American Pulsed Field type 1 and ribotype 027, usingpolymerase chain reaction).⁵

Costa Rica, an outbreak of CDAD occurred towards the end of 2008 and in the first semester of 2009. This study describes the epidemiologic, clinical and microbiological characteristics of that episode.

⁸

1 and 2).

Table 1), 63 were men (56%). The mean age was of 65,33 years (SD=16,63) and the age range varied from 16 to 93 years.

Thumbnail

Table 1

Canada, a developed country with high health indicators.^1,2,7

⁹

^10,11For the first time in Latin America the strain of C. difficile NAP1 was identified, responsible for this and other outbreaks in the world.^3,8

^{2, 12-14}The CDAD is more aggressive in the elderly, with a higher relapse frequency, and they also present a lower response to treatment, the disease causes a prolonged hospitalization and, it also is associated to a higher mortality.¹⁴The elderly population has several risk factors that make it particularly susceptible to C. difficile, like multidrug use with an extended use of antacids, antibiotics and laxatives, immunosenescence and comorbidities, ^12-14not considering the continuous ethical dilemmas that some of these patients represent.

^16-18

^1,2,18-22Among the undesirable effects of these drugs is the emergence of resistant bacteria, as well as the disturbance of normal bacterial flora, in these cases, intestinal flora´s delicate equilibrium is altered by the indiscriminate use of antibiotics and there is elimination of fundamental bacteria for intestinal homeostasis; so it generates destruction of bacterial flora, that is proven with fecal tests where a decrease is found in these patients. This destruction allows the proliferation of pathogenic bacteria, as C. difficile. Most of the patients (91%) had received 3 or more antibiotics, among which were included third generation cephalosporins, fluorochinolones and clindamycin, that have been related with this pathology.^21-22A study showed that the new fluorochinolones induced, in a model of a human intestine, the sporulation and an increase in the production of cytokinin in C. difficile, despite the resistance to these antibiotics, ²³ and epidemiologically they have been directly related with the outbreaks of this new strain.Pépin et al ²²evidenced in the outbreak analyzed in Canada, that the probability of developing CDAD was from 3 to 7 times greater if fluorochinolones were used, and from 1 to 3 times, if third generation cephalosporins were used. Similar relations were obtained with antibiotic therapy of a longer than five days duration. In the present study, the prolonged lapse of the antimicrobial therapy previous to the beginning of CDAD should call for reflection.

¹⁸as it is observed in this study. Again, it should be pointed out that most patients received antibiotics for very prolonged times while they were hospitalized.

^1,11,18This last data can be associated with the loss of proteins due to the diarrhea, because it behaves as a protein-losing enteropathy.²⁴

^16-24

^1-4

^10,17,21even when some authors doubt that the severity is exclusive to this strain. ^11,18,19

^25,26a consensus exists that in outbreaks where the hypervirulent strain is involved, patients must be treated aggressively from the onset, by using oral vancomycin for 2-3 weeks; these will lower the duration of the diarrhea as well as the complications associated with it. In some cases, intravenous metronidazole should be associated, since its bioavailability by oral administration in the intestine, is not high enough. With this study, it is not possible to elucidate which was the best therapeutic scheme, since it was a retrospective study.

^27,28During the outbreak, this therapy was used in three patients with satisfactory results.

^2,5-7and it is noticeable the there is a low recurrence and lethality associated directly to this pathology, contrary to the popular perception externalized by the local media at the time of the incident.

⁸demonstrated for the first time in Latin America, the presence of the hypervirulent strain of C. difficile NAP1, associated to epidemic outbreaks in several parts of the world.

Latin America, as the responsible agent in a group of patients. Thanks to the measures implemented, the emergency was controlled in a satisfactory way, as compared to outbreaks in other latitudes, where even hospitals had to be shut down.

References

1. Thielman NM y Wilson KH. Antibiotic -Associated Colitis In Mandell, Douglas, and Bennett´s Editors Principles and Practice ₆^th of Infectious Diseases Edition. PennsylvaniaChurchill Livingstone 2010; 1375-1387.
2. Freeman J, Bauer MP, Baines SD, Corver, J Fawley WN, Goorhuis B et al. The changing epidemiology of Clostridium difficile infections. Clin MicrobiolRev 2010; 23: 529-549.
3. Clements ACA, Soares Magalhaes, RJ Tatem, AJ Paterson, DL Riley TV. Clostridium difficile PCR ribotype 027: assessing the risks of further worldwide spread. Lancet Infect Dis2010; 10: 395-404.
4. Bartlett JG. Clostridium difficile infection: Historic review. Anaerobe2009; 15: 227-229.
5. McDonald CL, Killgore GE, Thompson A, Owens RC, Kazakova SV, Sambol SP et al. An Epidemic, toxin gene-variant strain of Clostridium difficile N EnglJ Med 2005; 353: 2433-2441.
6. Kelly CP y LaMont T. Clostridium difficile-more difficult than ever. N EnglJ Med 2008; 359: 1932-1940.
7. Gravel D Miller, M Simor, A Taylor, G Gardam, M McGeer A et al. Health care-associated Clostridium difficile infection in adults admitted to acute care hospitals in Canada: a Canadian nosocomial infection surveillance program study. Clin Infect Dis2009; 48: 568-576.
8. Quesada-Gómez, C Rodríguez, C Gamboa-Coronado, M Rodríguez-Cavallini, E Du T Mulvey MR et al. Emergence of Clostridium difficile NAP1 in Latin America. J Clin Microbiol2010; 48: 669-670.
9. Gerding D, MutoCA y Owens RC. Measures to control and prevent Clostridium difficile infection. Clin Inf Dis2008; 46: 43–49.
10. Loo V Poirier, L Miller, MA Oughton, M Libman, MD Michaud S. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N EnglJ Med 2005; 353: 2442-2449.
11. Hookman P y Barkin J. Clostridium difficile associated infection, diarrhea and colitis. World J Gastroenterol2009; 15: 1554-1580.
12. Jagai J y Naumova E. Clostridium difficile-associated disease in the elderly. United States Emerg Infect Dis2009; 15: 343-344.
13. Zilberberg MD, Shorr AF, Micek ST, Doherty JA y Kollef M H. Clostridium difficile-associated disease and mortality among the elderly critically ill. CritCare Med 2009; 37: 2583-2589.
14. Diggs NG y Surawicz CM. Clostridium difficile infection: still principally a disease of the elderly. Therapy 2010; 7: 295-301.
15. Cober ED y Malani P N. Clostridium difficile infection in the “oldest” old: clinical outcomes in patients aged 80 and older. J Am GeriatSoc 2009; 57: p 659-662.
16. Raveh D, Rabinowitz B, Breur GS, Rudensky B y Yinnon AM. Risk factors for Clostridium difficile toxin-positive nosocomial diarrhea. Int J AntimicrobAgents 2006; 28: 231-237.
17. Pépin J, Valiquette L y Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulentstrain in Quebec. CMAJ 2005; 173: 1037-1042.
18. Suneshide RH y McDonald LC. Clostridium difficile-associated disease. New challenges from an established pathogen. Clev ClinJ Med 2006; 73: p 187-197.
19. Blondeau J M. What have we learned about antimicrobial use and the risks for Clostridium difficile-associated diarrhoea? J Antimicrob Chemother2009; 63: 238-242.
20. Weiss K, Bergeron L, Bernatchez H, Goyette M, Savoie M y Thirion D. Clostridium difficile-associated diarrhoea rates and global antibiotic consumption in five Quebec institutions from 2001 to 2004. Int J Antimicrob Agents 2007; 30: 309-314.
21. Owens RC, Donskey CJ, Gaynes RP, Loo VG y Muto CA. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis2008; 46: S 19–31.
22. Pépin J, Saheb N, Coulombe MA, Alary ME, Corriveau SA, Leblanc M et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis2005; 41: 1254-1260.
23. Saxton K, BainesSD, Freeman J, O’Connor R y Wilcox MH. Effects of exposure of Clostridium difficile PCR Ribotypes 027 and 001 to fluoroquinolones in a human gut model. Antimicrob Agents Chemother2009; 53: 412-420.
24. Efron P y Mazuski J E. Clostridium difficile colitis. Surg ClinN Am 2009; 89: 483-500.
25.Bartlett JG.The case for vancomycin as the preferred drug for treatment of Clostridium difficile infection.Clin Infect Dis 2008;46: 1489-1492.
26. Cohen SH, Gerdin DN, Johnson S, Kelly CP, Loo V McDonald CL et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol2010; 31: 431-455.
27. Aslam S, Richard J, Hamill RJ y Musher DM. Treatment of Clostridium difficile-associated disease: old therapies and new strategies. Lancet Infect Dis2005; 5: 549–57.
28. Wilcox MH. Descriptive study of intravenous immunoglobulin for the treatment of recurrent Clostridium difficile diarrhea. J Antimicrob Chemother2004; 53: 882–884.

en_bart5

Date received: july 27, 2011 Date accepted: May 10, 2012

References

1. Thielman NM y Wilson KH. Antibiotic -Associated Colitis In Mandell, Douglas, and Bennett´s Editors Principles and Practice ₆^th of Infectious Diseases Edition. PennsylvaniaChurchill Livingstone 2010; 1375-1387.
2. Freeman J, Bauer MP, Baines SD, Corver, J Fawley WN, Goorhuis B et al. The changing epidemiology of Clostridium difficile infections. Clin MicrobiolRev 2010; 23: 529-549.
3. Clements ACA, Soares Magalhaes, RJ Tatem, AJ Paterson, DL Riley TV. Clostridium difficile PCR ribotype 027: assessing the risks of further worldwide spread. Lancet Infect Dis2010; 10: 395-404.
4. Bartlett JG. Clostridium difficile infection: Historic review. Anaerobe2009; 15: 227-229.
5. McDonald CL, Killgore GE, Thompson A, Owens RC, Kazakova SV, Sambol SP et al. An Epidemic, toxin gene-variant strain of Clostridium difficile N EnglJ Med 2005; 353: 2433-2441.
6. Kelly CP y LaMont T. Clostridium difficile-more difficult than ever. N EnglJ Med 2008; 359: 1932-1940.
7. Gravel D Miller, M Simor, A Taylor, G Gardam, M McGeer A et al. Health care-associated Clostridium difficile infection in adults admitted to acute care hospitals in Canada: a Canadian nosocomial infection surveillance program study. Clin Infect Dis2009; 48: 568-576.
8. Quesada-Gómez, C Rodríguez, C Gamboa-Coronado, M Rodríguez-Cavallini, E Du T Mulvey MR et al. Emergence of Clostridium difficile NAP1 in Latin America. J Clin Microbiol2010; 48: 669-670.
9. Gerding D, MutoCA y Owens RC. Measures to control and prevent Clostridium difficile infection. Clin Inf Dis2008; 46: 43–49.
10. Loo V Poirier, L Miller, MA Oughton, M Libman, MD Michaud S. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N EnglJ Med 2005; 353: 2442-2449.
11. Hookman P y Barkin J. Clostridium difficile associated infection, diarrhea and colitis. World J Gastroenterol2009; 15: 1554-1580.
12. Jagai J y Naumova E. Clostridium difficile-associated disease in the elderly. United States Emerg Infect Dis2009; 15: 343-344.
13. Zilberberg MD, Shorr AF, Micek ST, Doherty JA y Kollef M H. Clostridium difficile-associated disease and mortality among the elderly critically ill. CritCare Med 2009; 37: 2583-2589.
14. Diggs NG y Surawicz CM. Clostridium difficile infection: still principally a disease of the elderly. Therapy 2010; 7: 295-301.
15. Cober ED y Malani P N. Clostridium difficile infection in the “oldest” old: clinical outcomes in patients aged 80 and older. J Am GeriatSoc 2009; 57: p 659-662.
16. Raveh D, Rabinowitz B, Breur GS, Rudensky B y Yinnon AM. Risk factors for Clostridium difficile toxin-positive nosocomial diarrhea. Int J AntimicrobAgents 2006; 28: 231-237.
17. Pépin J, Valiquette L y Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulentstrain in Quebec. CMAJ 2005; 173: 1037-1042.
18. Suneshide RH y McDonald LC. Clostridium difficile-associated disease. New challenges from an established pathogen. Clev ClinJ Med 2006; 73: p 187-197.
19. Blondeau J M. What have we learned about antimicrobial use and the risks for Clostridium difficile-associated diarrhoea? J Antimicrob Chemother2009; 63: 238-242.
20. Weiss K, Bergeron L, Bernatchez H, Goyette M, Savoie M y Thirion D. Clostridium difficile-associated diarrhoea rates and global antibiotic consumption in five Quebec institutions from 2001 to 2004. Int J Antimicrob Agents 2007; 30: 309-314.
21. Owens RC, Donskey CJ, Gaynes RP, Loo VG y Muto CA. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis2008; 46: S 19–31.
22. Pépin J, Saheb N, Coulombe MA, Alary ME, Corriveau SA, Leblanc M et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis2005; 41: 1254-1260.
23. Saxton K, BainesSD, Freeman J, O’Connor R y Wilcox MH. Effects of exposure of Clostridium difficile PCR Ribotypes 027 and 001 to fluoroquinolones in a human gut model. Antimicrob Agents Chemother2009; 53: 412-420.
24. Efron P y Mazuski J E. Clostridium difficile colitis. Surg ClinN Am 2009; 89: 483-500.
25.Bartlett JG.The case for vancomycin as the preferred drug for treatment of Clostridium difficile infection.Clin Infect Dis 2008;46: 1489-1492.
26. Cohen SH, Gerdin DN, Johnson S, Kelly CP, Loo V McDonald CL et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol2010; 31: 431-455.
27. Aslam S, Richard J, Hamill RJ y Musher DM. Treatment of Clostridium difficile-associated disease: old therapies and new strategies. Lancet Infect Dis2005; 5: 549–57.
28. Wilcox MH. Descriptive study of intravenous immunoglobulin for the treatment of recurrent Clostridium difficile diarrhea. J Antimicrob Chemother2004; 53: 882–884.

en_bart5

Date received: july 27, 2011 Date accepted: May 10, 2012

Publication Dates

Publication in this collection
07 May 2013
Date of issue
Sept 2012

History

Received
27 July 2011
Accepted
10 May 2012

[1] 1. Thielman NM y Wilson KH. Antibiotic -Associated Colitis In Mandell, Douglas, and Bennett´s Editors Principles and Practice ₆^th of Infectious Diseases Edition. PennsylvaniaChurchill Livingstone 2010; 1375-1387.

[2] 2. Freeman J, Bauer MP, Baines SD, Corver, J Fawley WN, Goorhuis B et al. The changing epidemiology of Clostridium difficile infections. Clin MicrobiolRev 2010; 23: 529-549.

[3] 3. Clements ACA, Soares Magalhaes, RJ Tatem, AJ Paterson, DL Riley TV. Clostridium difficile PCR ribotype 027: assessing the risks of further worldwide spread. Lancet Infect Dis2010; 10: 395-404.

[4] 4. Bartlett JG. Clostridium difficile infection: Historic review. Anaerobe2009; 15: 227-229.

[5] 5. McDonald CL, Killgore GE, Thompson A, Owens RC, Kazakova SV, Sambol SP et al. An Epidemic, toxin gene-variant strain of Clostridium difficile N EnglJ Med 2005; 353: 2433-2441.

[6] 6. Kelly CP y LaMont T. Clostridium difficile-more difficult than ever. N EnglJ Med 2008; 359: 1932-1940.

[7] 7. Gravel D Miller, M Simor, A Taylor, G Gardam, M McGeer A et al. Health care-associated Clostridium difficile infection in adults admitted to acute care hospitals in Canada: a Canadian nosocomial infection surveillance program study. Clin Infect Dis2009; 48: 568-576.

[8] 8. Quesada-Gómez, C Rodríguez, C Gamboa-Coronado, M Rodríguez-Cavallini, E Du T Mulvey MR et al. Emergence of Clostridium difficile NAP1 in Latin America. J Clin Microbiol2010; 48: 669-670.

[9] 9. Gerding D, MutoCA y Owens RC. Measures to control and prevent Clostridium difficile infection. Clin Inf Dis2008; 46: 43–49.

[10] 10. Loo V Poirier, L Miller, MA Oughton, M Libman, MD Michaud S. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N EnglJ Med 2005; 353: 2442-2449.

[11] 11. Hookman P y Barkin J. Clostridium difficile associated infection, diarrhea and colitis. World J Gastroenterol2009; 15: 1554-1580.

[12] 12. Jagai J y Naumova E. Clostridium difficile-associated disease in the elderly. United States Emerg Infect Dis2009; 15: 343-344.

[13] 13. Zilberberg MD, Shorr AF, Micek ST, Doherty JA y Kollef M H. Clostridium difficile-associated disease and mortality among the elderly critically ill. CritCare Med 2009; 37: 2583-2589.

[14] 14. Diggs NG y Surawicz CM. Clostridium difficile infection: still principally a disease of the elderly. Therapy 2010; 7: 295-301.

[15] 15. Cober ED y Malani P N. Clostridium difficile infection in the “oldest” old: clinical outcomes in patients aged 80 and older. J Am GeriatSoc 2009; 57: p 659-662.

[16] 16. Raveh D, Rabinowitz B, Breur GS, Rudensky B y Yinnon AM. Risk factors for Clostridium difficile toxin-positive nosocomial diarrhea. Int J AntimicrobAgents 2006; 28: 231-237.

[17] 17. Pépin J, Valiquette L y Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulentstrain in Quebec. CMAJ 2005; 173: 1037-1042.

[18] 18. Suneshide RH y McDonald LC. Clostridium difficile-associated disease. New challenges from an established pathogen. Clev ClinJ Med 2006; 73: p 187-197.

[19] 19. Blondeau J M. What have we learned about antimicrobial use and the risks for Clostridium difficile-associated diarrhoea? J Antimicrob Chemother2009; 63: 238-242.

[20] 20. Weiss K, Bergeron L, Bernatchez H, Goyette M, Savoie M y Thirion D. Clostridium difficile-associated diarrhoea rates and global antibiotic consumption in five Quebec institutions from 2001 to 2004. Int J Antimicrob Agents 2007; 30: 309-314.

[21] 21. Owens RC, Donskey CJ, Gaynes RP, Loo VG y Muto CA. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis2008; 46: S 19–31.

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<b>Epidemiologic, clinical, and microbiologic description of an outbreak of Clostridium difficile associated diarrhea in Costa Rica</b>

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