An epidemic, toxin gene-variant strain of Clostridium difficile.
BACKGROUND
Recent reports suggest that the rate and severity of Clostridium difficile-associated disease in the United States are increasing and that the increase may be associated with the emergence of a new strain of C. difficile with increased virulence, resistance, or both.


METHODS
A total of 187 C. difficile isolates were collected from eight health care facilities in six states (Georgia, Illinois, Maine, New Jersey, Oregon, and Pennsylvania) in which outbreaks of C. difficile-associated disease had occurred between 2000 and 2003. The isolates were characterized by restriction-endonuclease analysis (REA), pulsed-field gel electrophoresis (PFGE), and toxinotyping, and the results were compared with those from a database of more than 6000 isolates obtained before 2001. The polymerase chain reaction was used to detect the recently described binary toxin CDT and a deletion in the pathogenicity locus gene, tcdC, that might result in increased production of toxins A and B.


RESULTS
Isolates that belonged to one REA group (BI) and had the same PFGE type (NAP1) were identified in specimens collected from patients at all eight facilities and accounted for at least half of the isolates from five facilities. REA group BI, which was first identified in 1984, was uncommon among isolates from the historic database (14 cases). Both historic and current (obtained since 2001) BI/NAP1 isolates were of toxinotype III, were positive for the binary toxin CDT, and contained an 18-bp tcdC deletion. Resistance to gatifloxacin and moxifloxacin was more common in current BI/NAP1 isolates than in non-BI/NAP1 isolates (100 percent vs. 42 percent, P<0.001), whereas the rate of resistance to clindamycin was the same in the two groups (79 percent). All of the current but none of the historic BI/NAP1 isolates were resistant to gatifloxacin and moxifloxacin (P<0.001).


CONCLUSIONS
A previously uncommon strain of C. difficile with variations in toxin genes has become more resistant to fluoroquinolones and has emerged as a cause of geographically dispersed outbreaks of C. difficile-associated disease.
McDonald
L Clifford
LC
Epidemiology and Laboratory Branch, Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, USA. cmcdonald1@cdc.gov
Killgore
George E
GE
Thompson
Angela
A
Owens
Robert C
RC
Kazakova
Sophia V
SV
Sambol
Susan P
SP
Johnson
Stuart
S
Gerding
Dale N
DN
D036002:ADP Ribose Transferases / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics; D015373:Bacterial Typing Techniques; D016360:Clostridioides difficile / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D003015:Clostridium Infections / Q000453:epidemiology / Q000382:microbiology*; D004196:Disease Outbreaks; D005819:Genetic Markers; D006801:Humans; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D000091402:Prohibitins; D012097:Repressor Proteins / Q000235:genetics; D014481:United States / Q000453:epidemiology; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005819:Genetic Markers; C000717331:PHB2 protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; C105615:TcdC protein, Clostridium difficile; D037521:Virulence Factors; D036002:ADP Ribose Transferases; C410164:actin-specific ADP-ribosyltransferase, Clostridium