Increase in Clostridium difficile-related mortality rates, United States, 1999-2004.Reported mortality rates from Clostridium difficile Clostridium difficile A common cause of bacterial colitis; it is the causative agent in 99% of pseudomembranous colitis, and 20-30% of antibiotic-associated diarrhea disease in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. increased from 5.7 per million population in 1999 to 23.7 per million in 2004. Increased rates may be due to emergence of a highly virulent strain of C. difficile. Rates were higher for whites than for other racial/ethnic groups. ********** Clostridium difficile is an anaerobic anaerobic /an·aer·o·bic/ (an?ah-ro´bik) 1. lacking molecular oxygen. 2. growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. , gram-positive bacillus bacillus (bəsĭl`əs), any rod-shaped bacterium or, more particularly, a rod-shaped bacterium of the genus Bacillus. Some bacterium in the genus cause disease, for example B. that can cause considerable disease, including diarrhea, colitis, and septicemia septicemia (sĕptĭsē`mēə), invasion of the bloodstream by virulent bacteria that multiply and discharge their toxic products. The disorder, which is serious and sometimes fatal, is commonly known as blood poisoning. , resulting in death (1). C. difficile-associated disease (CDAD CDAD Clostridium Difficile-Associated Diarrhea CDAD Component Data Administrator ) primarily affects persons [greater than or equal to] 65 years. Risk factors include residence in hospitals and long-term care facilities long-term care facility n. See skilled nursing facility. and the use of antimicrobial medications (1-3). Incidence of CDAD has been increasing, and severe cases are becoming more common (4,5). These changes in the incidence and severity of CDAD may be associated with the emergence of a more virulent strain of C. difficile bacteria (5,6). Death rates associated with C. difficile were reported to be increasing from 1999 to 2002 in the United States and from 2001 to 2005 in England and Wales England and Wales are both constituent countries of the United Kingdom, that together share a single legal system: English law. Legislatively, England and Wales are treated as a single unit (see State (law)) for the conflict of laws. (7,8). However, no trend analysis was conducted to evaluate the rate of increase. We incorporated mortality data for the United States through the year 2004 to conduct trend analyses of CDAD-related deaths and to examine demographic characteristics and coexisting conditions reported in deaths from C. difficile infection. The Study CDAD-related deaths were identified by using multiple cause-of-death data from national mortality records for 1999-2004. CDAD-related deaths were defined as all deaths for which the underlying cause of death or any of the contributing causes of death included the International Classification of Diseases, 10th revision (ICD-10) code A04.7 (enterocolitis enterocolitis /en·tero·co·li·tis/ (-ko-li´tis) inflammation of the small intestine and colon. antibiotic-associated enterocolitis due to C. difficile). Information about the size and demographic breakdown of the US population for each year during 1999-2004 was obtained from censal and intercensal year estimates with bridged race data (9,10). Age-adjusted mortality rates were calculated by using the age distribution of the 2000 US population as a standard (11). The US-population was divided into 5 racial/ethnic categories: white, Hispanic, Asian/Pacific Islander, black, and American Indian/Alaska Native. During 1999-2004, CDAD was reported as a cause of death for 20,642 persons. CDAD was reported as the underlying cause for 12,264 (59%) of these deaths. A total of 3,256 deaths were reported related to all other intestinal infectious diseases infectious diseases: see communicable diseases. combined (ICD-10 codes A00 to A09, excluding A047) over the same period. The median age of death for CDAD patients was 82 years. Age-adjusted mortality rates from CDAD were slightly higher for men than for women (Table) and were higher for whites than for any other racial/ethnic group. Most CDAD-related deaths occurred in hospitals (n = 16,557, 80%); 1,634 (8%) occurred in long-term care facilities, and 2,027 (10%) occurred at home. Common coexisting conditions for CDAD-related deaths included septicemia (n = 7,654, 37%), renal failure renal failure n. Acute or chronic malfunction of the kidneys resulting from any of a number of causes, including infection, trauma, toxins, hemodynamic abnormalities, and autoimmune disease, and often resulting in systemic symptoms, especially edema, (n = 4,786, 23%), pneumonia (n = 3,430, 17%), urinary tract infection urinary tract infection (UTI), n infection in one or more of the structures that make up the urinary system. Occurs more often in women and is most commonly caused by bacteria. (n = 1,496, 7%), and anemia (n = 785, 4%). HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. was reported for 81 CDAD-related deaths (<1%). However, among the 697 deaths reported in persons 25-54 years of age, HIV was reported for 72 (10%). The overall rate of C. difficile-related deaths during the study period was 12.2 deaths per million population. Mortality rates related to CDAD increased during the study period (Figure), rising from 5.7 deaths per million population in 1999 to 23.7 deaths per million population in 2004. Poisson regression In statistics, the Poisson regression model attributes to a response variable Y a Poisson distribution whose expected value depends on a predictor variable x, typically in the following way: n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. = 0.29-0.31) during the study period. [FIGURE OMITTED] Conclusions Due to the inclusion of CDAD-related deaths when CDAD was not reported as the underlying cause of death, reported death rates in this study were higher than those published in an earlier analysis of CDAD-related deaths in the United States (7). C. difficile is a cause of a substantial and increasing proportion of deaths in the United States and may be underrecognized as a cause of death. Little attention has been paid to C. difficile prevention; media and public health awareness efforts have focused largely on the prevention of disease from other intestinal pathogens such as Escherichia coli Escherichia coli (ĕsh'ərĭk`ēə kō`lī), common bacterium that normally inhabits the intestinal tracts of humans and animals, but can cause infection in other parts of the body, especially the urinary tract. or Salmonella spp. However, the incidence of deaths from C. difficile is greater than the extent of deaths from all other intestinal infectious diseases combined. C. difficile-related mortality rates were higher for whites than for other racial/ethnic groups. Racial/ethnic differences in insurance status and access to care (12) may render elderly whites more likely to receive treatment with antimicrobial drugs that put them at risk for C. difficile infection. However, genetic or other factors may also be involved, and further research is needed to determine the causes of racial/ethnic differences in C. difficile-related deaths. Previous research showed increases in CDAD-related mortality rates in the United States until 2002 (7,8). This analysis estimates the rate of increase at 35% per year, and shows that mortality rates continued to increase at least until 2004. Increases in incidence and deaths from CDAD may be associated with the emergence of a new and more virulent strain of C. difficile (5). The emergence of virulent strains of C. difficile makes continued assessment of mortality statistics important. Infection with C. difficile is associated with recent use of antimicrobial medications and with residence in hospitals. Most CDAD cases are acquired in healthcare settings (1), and as many as 90% of cases may be associated with antimicrobial drug use (2,3). High C. difficile death rates call attention to the importance of proper infection control practices in hospitals and long-term care facilities and the judicious use of antimicrobial medications. Further research is needed to explore current questions concerning which antimicrobial medications, if any, will lead to CDAD (13,14). Infections such as septicemia, pneumonia, and urinary tract infections were commonly reported in conjunction with C. difficile-related deaths. For some of these patients, the administration of antimicrobial medications to treat infections from other pathogens may have paved the way for infection with C. difficile. However, other risk factors are known, so that in many cases the careful use of antimicrobial agents may not be enough to prevent C. difficile infection. HIV infection was only reported in a small fraction of CDAD-related deaths. However, immunosuppression immunosuppression Suppression of immunity with drugs, usually to prevent rejection of an organ transplant. Its aim is to allow the recipient to accept the organ permanently with no unpleasant side effects. and the use of prophylactic antimicrobial drugs in persons with AIDS may increase the risk for CDAD (15), and the effects of HIV should not be overlooked. In persons 25-54 years of age, in whom HIV infection is most common, HIV infection was reported in approximately one tenth of CDAD-related deaths. Thus, HIV can considerably increase C. difficile death rates for demographic groups in which HIV prevalence is high. Death certificate data may underrepresent un·der·rep·re·sent tr.v. un·der·rep·re·sent·ed, un·der·rep·re·sent·ing, un·der·rep·re·sents To imply or suggest a lower amount, quantity, quality, or degree of than is actually present: the extent of CDAD-related deaths. This analysis was limited to deaths in which ICD-10 code A047 (enterocolitis due to C. difficile) was mentioned and may have failed to capture CDAD-related deaths in which colitis was not present. In addition, death certificate data may be affected by reporting error. Supplemental information such as decedents' medical histories was unavailable. No data were available regarding which strains of C. difficile were responsible for reported CDAD-related deaths. C. difficile is an underrecognized cause of severe illness and death. This analysis underscores the importance of CDAD as a public health problem and the increasing incidence of CDAD-related deaths in the United States. Mr Redelings is an epidemiology analyst with the Los Angeles County Department of Public Health. He previously served as a humanitarian worker in Sudan. His current research interests include the epidemiology of gastrointestinal infections and the prevention of disease in refugee situations. References (1.) Kelly CP, Pothoulakis C, LaMont TJ. Clostridium difficile colitis Clostridium difficile colitis Infectious disease Colonic infection by C difficile Clinical Some are asymptomic and become C difficile carriers; more commonly, diarrhea, abdominal pain, colitis, fever, vomiting dehydration; if severe, pseudomembranous . N Engl J Med. 1994;330:257-62. (2.) Bignardi GE. Risk factors for Clostridium difficile infection. J Hosp Infect. 1998;40:1-15. (3.) Barbut F, Petit JC. Epidemiology of Clostridium clostridium Any of the rod-shaped, usually gram-positive bacteria (see gram stain) that make up the genus Clostridium. They are found in soil, water, and the intestinal tracts of humans and other animals. Some species grow only in the complete absence of oxygen. difficile-associated infections. Clin Microbiol Infect. 2001;7:405-10. (4.) McDonald LC, Banerjee S, Jernigan DB. Increasing incidence of Clostridium difficile-associated disease in US acute care hospitals, 1993-2001. Presented at the 14th Annual Scientific Meeting of the Society for Healthcare Epidemiology in America; Apr 17-20, 2004; Philadelphia. Abstract 67. (5.) Pepin J, Valiquettte L, Alary a·la·ry adj. Variant of alar. Adj. 1. alary - having or resembling wings aliform, wing-shaped, alar biological science, biology - the science that studies living organisms ME. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ CMAJ Canadian Medical Association Journal . 2004; 171:466-72. (6.) Kuijper EJ, Coignard B, Tull P, ESCMID ESCMID European Society of Clinical Microbiology and Infectious Diseases Study Group for Clostridium difficile; EU Member States; and European Centre for Disease Prevention and Control The European Centre for Disease Prevention and Control (ECDC) is an agency of the European Union (EU), located in Stockholm (Solna Municipality), Sweden. The ECDC has been created to help strengthen Europe’s defences against infectious diseases, such as influenza, (ECDC ECDC Easy CD Creator (Roxio) ECDC European Centre for Disease Prevention and Control ECDC Economic Cooperation Among Developing Countries (Group of 77 countries) ). Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect. 2006; 12(Suppl 6):2-18. (7.) Wysowski DK. Increase in deaths related to enterocolitis due to Clostridium difficile in the United States, 1999-2002. Public Health Rep. 2006;121:361-2. (8.) Deaths involving MRSA MRSA Methicillin-resistant Staphylococcus aureus. See MARSA. and Clostridium difficile continue to rise. Health Stat Q. 2007; Press release: 1-3. (9.) National Center for Health Statistics National Center for Health Statistics (NCHS) is part of the Centers for Disease Control and Prevention (CDC), which is part of the United States Department of Health and Human Services. NCHS is the United States' principal health statistics agency. . Bridged-race intercensal estimates of the July 1, 1990-July 1, 1999, United States resident population by county, single-year of age, sex, race, and Hispanic origin. [cited 2007 Mar 30]. Available from http://www.cdc.gov/ nchs/about/major/dvs/popbridge/datadoc.htm#inter1 (10.) National Center for Health Statistics. Estimates of the July 1, 2000-July 1, 2004, United States resident population from the vintage 2003 postcensal series by year, county, age, sex, race, and Hispanic origin. [cited 2007 Mar 30]. Available from http://www.cdc.gov/ nchs/about/major/dvs/popbridge/datadoc.htm#inter1 (11.) Anderson RN, Rosenberg HM. Age standardization of death rates: implementation of the year 2000 standard. Natl Vital Stat Rep. 1998;47:1-16, 20. (12.) Adams PF, Barnes PM. Summary health statistics for the U.S. population: National Health Interview Survey, 2004. Vital Health Star 10. 2006;229:1-104. (13.) Dhalla IA, Mamdani MM, Simor AE, Kopp A, Rohon PA, Juurlink DN. Are broad-spectrum fluoroquinolones more likely to cause Clostridium difficile-associated disease? Antimicrob Agents Chemother. 2006;50:3216-9. (14.) Gaynes R, Rimland Rimland is the maritime fringe of a country or continent; in particular, the densely populated western, southern, and eastern edges of the Eurasian continent. According to Nicholas John Spykman, who revisited Halford Mackinder's concepts of geopolitics, the Rimland is that D, Killum E, Lowery low·er·y also lour·y adj. Overcast; threatening. HK, Johnson TM, Killgore G, et al. Outbreak of Clostridium difficile infection in a long-term care facility; association with gatifloxacin use. Clin Infect Dis. 2004;38:640-5. (15.) Sanchez TH, Brooks JT, Sullivan PS, Juhasz M, Mintz E, Sworkin MS, et al. Bacterial diarrhea in persons with HIV infection, United States, 1992-2002. Clin Infect Dis. 2005;41:1621-7. Address for correspondence: Matthew D. Redelings, 313 N Figueroa 127, Los Angeles, CA 90012, USA; email: mredelings@dhs.co.la.ca.us Matthew D. Redelings, * Frank Sorvillo, * ([dagger]) and Laurene Mascola * * Los Angeles County Department of Public Health, Los Angeles, California, USA; and ([dagger]) University of California The University of California has a combined student body of more than 191,000 students, over 1,340,000 living alumni, and a combined systemwide and campus endowment of just over $7.3 billion (8th largest in the United States). Los Angeles-School of Public Health, Los Angeles, California, USA
Table. Demographic characteristics of patients with Clostridium
difficile-related deaths, United States, 1999-2004
Age-
C. difficile- adjusted
related mortality
deaths, rate/million
Demographic group no. (%) population
Sex
Female 12,468 (60) 11.8
Male 8,174 (60) 12.7
Race/ethnicity
White 18,534 (90) 12.9
Hispanic 602 (3) 7.2
Black 1,304 (6) 9.3
Asian/Pacific Islander 139 (1) 3.5
American Indian/Alaska 63 (<1) 7.9
Native
Age group, y
<1 17 (<1) 0.7 *
1-4 11 (<1) 0.1 *
5-14 12 (<1) 0.1 *
15-24 24 (<1) 0.1 *
25-34 62 (<1) 0.3 *
35-44 171 (<1) 0.6 *
45-54 464 (1) 2.0 *
55-64 1,159 (2) 7.6 *
65-74 3,238 (16) 29.3 *
75-84 7,859 (38) 104.0 *
[greater than or 7,623 (37) 287.1 *
equal to] 85
Total 20,642 12.2
* This statistic is not age-adjusted because it only pertains
to 1 age group.
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