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Why were molecular studies not considered to classify Clostridium difficile isolates implicated in an outbreak?

To the Editor:

We read with interest the article, "Clostridium difficile outbreak in Costa Rica: control actions and associated factors," by Roy A. Wong-McClure and colleagues, recently published by this journal (1).

This work is of great value because it broadens the scarce knowledge regarding infections caused by C. difficile in hospitals in Latin America (2). It describes the measures taken for a 4-month C. difficile hospital diarrhea outbreak, and confirms that age > 59 years, hospitalization for 7 days or more, diabetes or chronic kidney failure, and therapy with ceftazidime and cefotaxime are risk factors associated with C. difficile associated disease (CDAD), as previously reported (3). On the other hand, despite the authors' explanation, the lack of association between CDAD and the administration of fluoroquinolones is noteworthy as it contradicts previous studies (3).

Our laboratory experience with C. difficile (4-5) has led us to confirm that strict procedures should be followed in order to achieve high cultivation rates from clinical samples. Thus, it would be interesting to know the isolation rate obtained by the authors, and to verify if all "toxin-positive isolates were confirmed by culture," especially since no enrichment procedure was used--contrary to what is recommended (6). In addition, the authors should clarify the number of isolates studied, so that readers might corroborate whether the isolates analyzed were representative of the outbreak.

Since no references are given in the laboratory analysis section, it is not clear whether tcdC deletions were detected by molecular methods. This information is important because there is considerable controversy regarding the role of these mutations in the toxin hyper production of epidemic strains (7).

The authors state that the isolates were non-BI strains characterized by the presence of the tcdA and tcdB genes. However, this information is somewhat vague from an epidemiological standpoint. It would be interesting to learn the intraspecific diversity of C. difficile in the outbreak, so as to compare it with the diversity of pulsotypes that we have previously found in another Costa Rican hospital (4) and to clarify if there were dominant pulsotypes. This information is crucial in light of our most recent studies, which reveal differences in the amounts of toxins produced by autochtonous pulsotypes (unpublished results).

Evelyn Rodriguez-Cavallini

Maria del Mar Gamboa Coronado

Cesar Rodriguez Sanchez

Carlos Quesada Gomez

Laboratorio de Investigacion en Bacteriologia

Anaerobia y Centro de Investigacion en

Enfermedades Tropicales

Facultad de Microbiologia

Universidad de Costa Rica

San Jose, Costa Rica



(1.) Wong-McClure RA, Guevara-Rodriguez M, Abarca-Gomez L, Solano-Chinchilla A, Marchena-Picado M, O'Shea M, et al. Clostridium difficile outbreak in Costa Rica: control actions and associated factors. Rev Panam Salud Publica. 2012;32(6):413-8 .

(2.) Balassiano IT, Yates EA, Domingues RM, Ferreira EO. Clostridium difficile: a problem of concern in developed countries and still a mystery in Latin America. J Med Microbiol. 2012;61(2):169-79.

(3.) Henrich TJ, Krakower D, Bitton A, Yokoe DS. Clinical risk factors for severe Clostridium difficile-associated disease. Emerg Infect Dis. 2009;15(3):415-22.

(4.) Zumbado-Salas R, Gamboa-Coronado MM, Chaves-Olarte E, Rodriguez-Cavallini E. Clostridium difficile in adults patients with nosocomial diarrhea in a Costa Rican hospital. Am J Trop Med Hyg. 2008;79(2):164-5.

(5.) Quesada-Gomez C, Rodriguez C, Gamboa-Coronado MM, Rodriguez-Cavallini E, Du T, Mulvey MR, et al. Emergence of Clostridium difficile NAP1 in Latin America. J Clin Microbiol. 2010;48(2):669-70.

(6.) Miller M, Gravel D, Mulvey M, Taylor G, Boyd D, Simor A, et al. Health care-associated Clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality. Clin Infect Dis. 2010;50:194-201.

(7.) Murray R, Boyd D, Levett PN, Mulvey MR, Alfa MJ. Truncation in the tcdC region of the Clostridium difficile PathLoc of clinical isolates does not predict increased biological activity of toxin B or toxin A. BMC Infect Dis. 2009;9:103.

Response to Rodriguez-Cavallini's et al. letter to the editor

To the Editor:

We are pleased that Rodriguez-Cavallini and colleagues have recognized our paper, "Clostridium difficile outbreak in Costa Rica: control actions and associated factors," for broadening the literature on C. difficile associated disease (CDAD) epidemiology and prevention in Latin America (1).

As to the contradiction mentioned with regards to the study results, it is important to consider that a diverse array of antibiotics can be associated with CDAD. Our study results are in agreement with the Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update (2), which includes restriction of antimicrobial use as cephalosporins, with high recommendation strength based on quality of evidence.

For our study, samples were collected from all affected patients rather than from a subset of cases during the outbreak. When comparing our results with those cited in existing literature in Latin America and in Costa Rica, it is important to consider that the local epidemiological profile of C. difficile at other centers may vary considerably from that of the hospital in this study. Also, it should be noted that the main objective of the study was to describe the infection control strategies implemented during the outbreak and to determine factors associated with C. difficile infection. The determination of specific molecular features of C. difficile was not a main focus of the investigation.

Finally, we commend the invaluable effort of the Laboratorio de Investigacion en Bacteriologia Anaerobia (LIBA) of the University of Costa Rica in contributing to the existing knowledge of autochthonous C. difficile pulsotypes. Given the inherent diversity of Costa Rican health centers, we feel it is extremely important to incorporate the work of LIBA into the country's routine surveillance of C. difficile to increase knowledge regarding this critical pathogen.

Roy A. Wong-McClure

Leandra Abarca-Gomez

Xiomara Badilla-Vargas

Salud Colectiva, Subarea de Epidemiologia Caja Costarricense de Seguro Social

San Jose, Costa Rica


Moraima Guevara-Rodriguez

Antonio Solano-Chinchilla

Margarita Marchena-Picado

Hospital Calderon Guardia Caja Costarricense de Seguro Social

San Jose, Costa Rica

Michele O'Shea

University of Arizona

College of Medicine

Phoenix, Arizona

United States of America


(1.) Wong-McClure RA, Guevara-Rodriguez M, Abarca-Gomez L, Solano-Chinchilla A, Marchena-Picado M, O'Shea M, et al. Clostridium difficile outbreak in Costa Rica: control actions and associated factors. Rev Panam Salud Publica. 2012;32(6): 413-8.

(2.) Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, 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 Epidemiol. 2010;31(5):431-55.
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Article Details
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Title Annotation:Letters/Cartas
Author:Rodriguez-Cavallini, Evelyn; Coronado, Maria del Mar Gamboa; Sanchez, Cesar Rodriguez; Gomez, Carlos
Publication:Revista Panamericana de Salud Publica
Article Type:Letter to the editor
Date:Nov 1, 2013
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