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Estimating risk of C. difficile transmission from PCR positive but cytotoxin negative cases.

Kamboj M, Babady NE, Marsh JW, Schlackman JL, Son C, Sun J, Eagan J, Tang YW, Sepkowitz K - PLoS ONE (2014)

Bottom Line: CYT -/PCR + cases had a higher median Ct value of detection compared to CYT+/PCR + cases (28.2 vs 22.5; p = 0.01).Among 25 strains that were genetically related, 9/11 isolates in this dominant cluster were positive by CYT compared to 4/14 in non-dominant clusters (p = 0.02).However, the risk of transmission of C. difficile from CYT +/PCR+ cases may be higher than those that are CYT-/PCR+.

View Article: PubMed Central - PubMed

Affiliation: Infection Control Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America ; Infectious Diseases Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.

ABSTRACT

Background: The use of molecular methods to diagnose Clostridium difficile infection (CDI) has improved diagnostic yield compared to conventional methods. However, PCR testing can detect colonization and has introduced several practical challenges pertaining to need for treatment and isolation of cases.

Methods: For all new cases detected by real-time PCR, concurrent cytotoxin assay was performed and genetic characterization with MLVA (multi-locus variable number tandem repeat analysis) was done to determine relatedness. We used PCR cycle threshold (Ct) of detection as surrogate marker for bacterial burden in stool.

Results: Overall, 54 cases of CDI were detected during the study period. 42 were concurrently tested by CYT and characterized by MLVA .MLVA analysis revealed marked genetic diversity with no ongoing outbreaks; four cases were due to NAP1 strain. CYT -/PCR + cases had a higher median Ct value of detection compared to CYT+/PCR + cases (28.2 vs 22.5; p = 0.01). Among 25 strains that were genetically related, 9/11 isolates in this dominant cluster were positive by CYT compared to 4/14 in non-dominant clusters (p = 0.02).

Conclusion: CYT-/PCR+ cases contribute to hospital based transmission. However, the risk of transmission of C. difficile from CYT +/PCR+ cases may be higher than those that are CYT-/PCR+.

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Related in: MedlinePlus

Minimum spanning tree of MLVA data from study isolates (n = 47).Letter symbol in the center of the circle represents the results for testing by cytotoxin assay for 42 samples included in the analysis (C + and C −). Five samples were not tested by CYT (NT). Each circle represents a distinct MLVA type and numbers between the circles represent the STRD [Summed tandem repeat difference]. Isolates with a STRD<10 are highlighted in colored clouds representing clusters (genetically related clonal complexes). tcdC sequencing is depicted by color coding within circles with tcdC 1 (corresponding to NAP1) strain represented in red (reference in right corner).
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pone-0088262-g001: Minimum spanning tree of MLVA data from study isolates (n = 47).Letter symbol in the center of the circle represents the results for testing by cytotoxin assay for 42 samples included in the analysis (C + and C −). Five samples were not tested by CYT (NT). Each circle represents a distinct MLVA type and numbers between the circles represent the STRD [Summed tandem repeat difference]. Isolates with a STRD<10 are highlighted in colored clouds representing clusters (genetically related clonal complexes). tcdC sequencing is depicted by color coding within circles with tcdC 1 (corresponding to NAP1) strain represented in red (reference in right corner).

Mentions: The results of MLVA typing of the study cohort are shown in Figure 1 along with results of CYT testing. For 42 isolates that were tested by CYT and characterized by MLVA, 23 were positive by CYT and 25 were genetically related. Among the 25 strains that were genetically related, 13 were positive by CYT compared to 10/17 strains that were unrelated (p = 0.3).One dominant cluster accounted for almost half of all the related strains (n = 11); isolates within this cluster are related by MLVA but are not part of an outbreak (8). Rather, the strain corresponds to common genetic lineages as defined by tcdC genotyping and represent endemic disease in the hospital setting. 9/11 isolates in this dominant cluster were positive by CYT compared to 4/14 in non-dominant clusters (p = 0.01).


Estimating risk of C. difficile transmission from PCR positive but cytotoxin negative cases.

Kamboj M, Babady NE, Marsh JW, Schlackman JL, Son C, Sun J, Eagan J, Tang YW, Sepkowitz K - PLoS ONE (2014)

Minimum spanning tree of MLVA data from study isolates (n = 47).Letter symbol in the center of the circle represents the results for testing by cytotoxin assay for 42 samples included in the analysis (C + and C −). Five samples were not tested by CYT (NT). Each circle represents a distinct MLVA type and numbers between the circles represent the STRD [Summed tandem repeat difference]. Isolates with a STRD<10 are highlighted in colored clouds representing clusters (genetically related clonal complexes). tcdC sequencing is depicted by color coding within circles with tcdC 1 (corresponding to NAP1) strain represented in red (reference in right corner).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921148&req=5

pone-0088262-g001: Minimum spanning tree of MLVA data from study isolates (n = 47).Letter symbol in the center of the circle represents the results for testing by cytotoxin assay for 42 samples included in the analysis (C + and C −). Five samples were not tested by CYT (NT). Each circle represents a distinct MLVA type and numbers between the circles represent the STRD [Summed tandem repeat difference]. Isolates with a STRD<10 are highlighted in colored clouds representing clusters (genetically related clonal complexes). tcdC sequencing is depicted by color coding within circles with tcdC 1 (corresponding to NAP1) strain represented in red (reference in right corner).
Mentions: The results of MLVA typing of the study cohort are shown in Figure 1 along with results of CYT testing. For 42 isolates that were tested by CYT and characterized by MLVA, 23 were positive by CYT and 25 were genetically related. Among the 25 strains that were genetically related, 13 were positive by CYT compared to 10/17 strains that were unrelated (p = 0.3).One dominant cluster accounted for almost half of all the related strains (n = 11); isolates within this cluster are related by MLVA but are not part of an outbreak (8). Rather, the strain corresponds to common genetic lineages as defined by tcdC genotyping and represent endemic disease in the hospital setting. 9/11 isolates in this dominant cluster were positive by CYT compared to 4/14 in non-dominant clusters (p = 0.01).

Bottom Line: CYT -/PCR + cases had a higher median Ct value of detection compared to CYT+/PCR + cases (28.2 vs 22.5; p = 0.01).Among 25 strains that were genetically related, 9/11 isolates in this dominant cluster were positive by CYT compared to 4/14 in non-dominant clusters (p = 0.02).However, the risk of transmission of C. difficile from CYT +/PCR+ cases may be higher than those that are CYT-/PCR+.

View Article: PubMed Central - PubMed

Affiliation: Infection Control Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America ; Infectious Diseases Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.

ABSTRACT

Background: The use of molecular methods to diagnose Clostridium difficile infection (CDI) has improved diagnostic yield compared to conventional methods. However, PCR testing can detect colonization and has introduced several practical challenges pertaining to need for treatment and isolation of cases.

Methods: For all new cases detected by real-time PCR, concurrent cytotoxin assay was performed and genetic characterization with MLVA (multi-locus variable number tandem repeat analysis) was done to determine relatedness. We used PCR cycle threshold (Ct) of detection as surrogate marker for bacterial burden in stool.

Results: Overall, 54 cases of CDI were detected during the study period. 42 were concurrently tested by CYT and characterized by MLVA .MLVA analysis revealed marked genetic diversity with no ongoing outbreaks; four cases were due to NAP1 strain. CYT -/PCR + cases had a higher median Ct value of detection compared to CYT+/PCR + cases (28.2 vs 22.5; p = 0.01). Among 25 strains that were genetically related, 9/11 isolates in this dominant cluster were positive by CYT compared to 4/14 in non-dominant clusters (p = 0.02).

Conclusion: CYT-/PCR+ cases contribute to hospital based transmission. However, the risk of transmission of C. difficile from CYT +/PCR+ cases may be higher than those that are CYT-/PCR+.

Show MeSH
Related in: MedlinePlus