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Influence of gender on outcomes of healthcare-associated C. difficile infections

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Alyssa Bernardo

on 15 August 2013

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Transcript of Influence of gender on outcomes of healthcare-associated C. difficile infections

Alyssa Bernardo
PHS Graduate Seminar
Oct. 3, 2012

Association between gender and outcomes of C. difficile infections
Identify groups at elevated risk for morbidity and mortality from healthcare-associated infections
Broader purpose:
Methods
Addressing study question
Do outcomes of CDI episodes differ by gender?
4. Insert results here
Possible explanations
Differences in treatment received
Differences in hospitalization history
Other confounders
Age
Obesity
Statins
PPIs
Type or duration of antibiotics
Recent hospital stay
Delay in diagnosis
Recurrent CDI
Immuno-compromised status
Gender
CDI Outcomes
Recurrent CDI
CDI
Treatment
Age
Smoking
Obesity
If so...
Biological differences that influence C. diff. pathogenesis
Comorbidity
History of hospitalization
Concurrent treatment
Investigate whether outcomes of healthcare-associated C. difficile infectious episodes differ between men and women
Study purpose:
Proton-pump inhibitors
Acid suppression
May be more often prescribed to men than to women
Inform preventative interventions and medical treatments
Reduce morbidity and mortality from healthcare-associated infections
paraphrased from some wise person
Since obesity affects the natural composition and distribution of your microflora
Background
Every year in the US, Clostridium difficile is responsible for...
Pathogenesis of CDI
Rationale for study
Next steps
Finalizing covariate list
2. Extracting records
3.
1.
Rupnik, Wilcox, Gerding. Clostridium difficile infection: New developments in epidemiology and pathogenesis. Nature Reviews: Microbiology 2009; 7(7):526-536.
1. External insult
2. Colonization
Spores germinate in terminal ileus
Bacteria adhere to mucosal barrier
Toxins produced
3. Intestinal cell
barrier disrupted
4. Fluid loss and
inflammation
Diarrhea
Fever
Inflammatory lesions
Outcomes
Public health significance
Predictors
Other demographics
2011
2012
Retrospective cohort
All UWHC inpatients from 2011-2012 who were diagnosed with a C. difficile infection
Study population:
Medical chart review
Gender
Other demographics:
Smoking status
Obesity
Race
Age
Prior ICU care
Prior care for CDI
Surgical history
Charlson's Index
HIV, Type II diabetes, CKD, liver disease
Comorbidity
History of hospitalization
Treatment
and antibiotics
Type
Duration
Concommitant
Delay in diagnosis
Mortality
Mortality attributable to CDI
All-cause 1-yr mortality
Symptom duration
Length of hospital stay
Severity score for CDI
1 pt. each for:
Temp >= 38.4
Albumin < 2.5 g/DL or WBC > 15

Based on worst value within 48 hours of CDAD diagnosis
Modified Zar Score (0-2):
Pictured right: Analysis
Statins
PPIs
Concommitant
antibiotics
Metronidazole
Vancomycin
Rifampin
Rifaximin
Conceptual model
Rupnik, Wilcox, Gerding. Clostridium difficile infection: New developments in epidemiology and pathogenesis. Nature Reviews: Microbiology 2009; 7(7):526-536.
Clinical practice guidelines for C. difficile infection in adults: 2010 update by SHEA and IDSA. Infection Control and Hospital Epidemiology 2010; 31(5):431-455.
Vital signs: Preventing Clostridium difficile infections. Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. March 9, 2012: 61(09);157-162.
Kyne L, Hamel MB, Polavaram R, Kelly C. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clinical Infectious Disease 2002; 34(3):346-353.
Johnson S, Clabots CR, Linn FV, Olson MM, Peterson LR, Gerding DN. Nosocomial Clostridium difficile colonisation and disease. Lancet 1990; 336(8707):97-100.
Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. New England Jrnl of Med. 1994; 330(4):257-262.
Mylonakis E, Ryan ET, Calderwood SB. Clostridium difficile-associated diarrhea: A review. Archive of Internal Med. 2001; 161(4):525-533.
References
Nasia Safdar
Ajay Sethi
Ron Gangnon
Susan Valentine
Adam Dundon
Linda McKinley
Megan Duster
Simone Warrack
Inf. Disease Dept.
Dept. of Population
Health Sciences
Acknowledgements
"Not so many relationships that the model becomes useless... and not so few that the model becomes useless"
Outcomes
Mortality
All-cause 1-yr mortality
Mortality attributable to CDI
Symptom duration
Length of hospital stay
Severity score for CDI
1 pt. each for age > 60, temp 38.4, albumin < 2.5 or WBC > 15 (based on worst value) within 48 hours of CDAD diagnosis
Zar Score (0-3):
Logistic regression
Linear regression
Survival analysis
Clinical practice guidelines for C. difficile infection in adults: 2010 update by SHEA and IDSA. Infection Control and Hospital Epidemiology 2010; 31(5):431-455.
Determining CDI classification
500,000 infections
20,000 deaths
1.1 billion in healthcare costs
Major infectious cause of healthcare-associated diarrhea
at least 25% of cases
Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. New England Jrnl of Med. 1994; 330(4):257-262.
Mylonakis E, Ryan ET, Calderwood SB. Clostridium difficile-associated diarrhea: A review. Archive of Internal Med. 2001; 161(4):525-533.
Kyne L, Hamel MB, Polavaram R, Kelly C. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clinical Infectious Disease 2002; 34(3):346-353.
C. difficile colonization
1-13%
50%
<1 wk.
>4 wks.
13-50%
1-4 wks.
Johnson S, Clabots CR, Linn FV, Olson MM, Peterson LR, Gerding DN. Nosocomial Clostridium difficile colonisation and disease. Lancet 1990; 336(8707):97-100.
CDI Classification
Healthcare-onset
Community-onset
Healthcare-associated
Community-associated
CO-HCFA
HO-CA
CA-CDI
HO-HCFA
(cc) image by anemoneprojectors on Flickr
CDC MMWR, March 2012
Clostridium difficile infection (CDI) is a common and sometimes fatal health-care–associated infection.

The incidence, deaths, and excess health-care costs resulting from CDIs in hospitalized patients are all at historic highs."

McFarland LV, Surawicz CM, Stamm WE. Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients. Journal of Infectious Diseases 1990; 162(3):678-684.
Marra AR, Edmond MB, Wenzel RP, Bearman GM. Hospital-acquired Clostridium difficile-associated disease in the intensive care unit setting: Epidemiology, clinical course and outcome. BMC Infectious Diseases 2007; 7:42-47.
Moore CL, Hingwe A, Donabedian SM, Perri MB, Davis SL, Haque NZ, Reyes K, Vager D, Zervos MJ. Comparative evaluation of epidemiology and outcomes of methicillin-resistant Staphylococcus aureus (MRSA) USA300 infections causing community- and healthcare-associated infections. International Journal of Antimicrobial Agents 2009; 34(2):148-155.
Hidron AI, Kourbatova EV, Halvosa JS, Terrell BJ, McDougal LK, Tenover FC, Blumberg HM, King MD. Risk factors for colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to an urban hospital: Emergence of community-associated MRSA nasal carriage. Clinical Infectious Diseases 2005; 41(2):159-166.
Gender not identified as a significant risk factor for CDI acquisition
Limited research examining the impact of gender on outcomes of CDI
McFarland LV, Surawicz CM, Stamm WE. Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients. Journal of Infectious Diseases 1990; 162(3):678-684.
Marra AR, Edmond MB, Wenzel RP, Bearman GM. Hospital-acquired Clostridium difficile-associated disease in the intensive care unit setting: Epidemiology, clinical course and outcome. BMC Infectious Diseases 2007; 7:42-47.
Gender and C. diff.
Gender and MRSA
Males significantly more likely to be...
Moore CL, Hingwe A, Donabedian SM, Perri MB, Davis SL, Haque NZ, Reyes K, Vager D, Zervos MJ. Comparative evaluation of epidemiology and outcomes of methicillin-resistant Staphylococcus aureus (MRSA) USA300 infections causing community- and healthcare-associated infections. International Journal of Antimicrobial Agents 2009; 34(2):148-155.
Colonized with MRSA
Infected with MRSA
Hidron AI, Kourbatova EV, Halvosa JS, Terrell BJ, McDougal LK, Tenover FC, Blumberg HM, King MD. Risk factors for colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to an urban hospital: Emergence of community-associated MRSA nasal carriage. Clinical Infectious Diseases 2005; 41(2):159-166.
28,000 admissions/yr
100-200 cases per year among UWHC inpatients
Increasing CDI
"
Incidence of C. difficile infections
Fig 1. Prevalence of Clostridium difficile colitis presented as the hospital discharge rate for patients with either a principal or a secondary diagnosis of C difficile colitis.
Fig 3. Clostridium difficile-associated disease incidence, Singapore, 2001-2006.
Fig 2. Incidence of Clostridium difficile-associated disease per 100,000 inpatients upon discharge from hospitals in Germany.
Ricciardi R, Rothenberger DA, Madoff RD, Baxter NN. Increasing prevalence and severity of Clostridium difficile colitis in hospitalized patients in the United States. Archives of Surgery 2007; 142(7):624-631.
Vonberg RP, Schwab F, Gastmeier P. Clostridium difficile in discharged inpatients, Germany [letter]. Emerg Infect Dis [serial on the Internet]. 2007 Jan [Sept. 30, 2012]. Available from http://wwwnc.cdc.gov/eid/article/13/1/06-0611.htm
Suggested citation for this article: Lim PL, Barkham TMS, Ling LM, Dimatatac F, Alfred T, Ang B. Increasing incidence of Clostridium difficile–associated disease, Singapore [letter]. Emerg Infect Dis [serial on the Internet]. 2008 Sept [Sept. 30, 2012]. Available from http://wwwnc.cdc.gov/eid/article/14/9/07-0043.htm
1999
5.7 deaths per million
23.7 deaths per million
2004
US Population
Ricciardi R, Rothenberger DA, Madoff RD, Baxter NN. Increasing prevalence and severity of Clostridium difficile colitis in hospitalized patients in the United States. Archives of Surgery 2007; 142(7):624-631.
Fig. 4. Case fatality for patients with either a principal or a secondary diagnosis of Clostridium difficile colitis.
Redelings MD, Sorvillo F, Mascola L. Increase in Clostridium difficile–related mortality rates, United States, 1999–2004. Emerg Infect Dis [serial on the Internet]. 2007 Sep [date cited]. Available from http://wwwnc.cdc.gov/eid/article/13/9/06-1116.htm
"Results of the study showed that the incidence of C.difficile infection (CDI) in children was more than 12 times higher between 2004 and 2009, compared to the period 1991-1997 (32.6 cases per 100,000 vs. 2.6). In addition, 75 percent of cases were "community-acquired," meaning that the patients had not been hospitalized for at least four weeks prior to contracting C. difficile. "
Population-based cohort study in children
Mayo Clinic (2012, May 21). Increasing incidence of clostridium difficile infection (c. Diff) challenges common beliefs about its origins. ScienceDaily. Retrieved October 1, 2012, from http://www.sciencedaily.com/releases/2012/05/120521132619.htm
1991-1997
2004-2009
2.6 cases per 100,000
32.6 cases per 100,000
Presented May 2012
Clostridium difficile:
Can cause diarrhea and other symptoms
In moderate to severe cases:
Fever
Abdominal pain
Nausea
Colotis
Spore-forming bacteria
Main route of transmission is fecal-oral
Maureen Durkin
Case fatality
1. To examine the association between gender and mortality attributable to CDI among patients with CDI.

2. To examine the association between gender and length of hospital stay, duration of symptoms, and Zar score among patients with CDI.
Specific Aims
.
10
3
May want to rethink using linear regression, since strictly speaking, the Zar severity score is discrete, not continuous.
Highlight antibiotics as the key predisposing factor for C. diff infection - conceptual model can be revised to reflect this (instead of lumping antibiotic use in together with 'history of hospitalization'-related predictors)
Can look at 'hotspots' or clumping to control for area of hospital
Can look at prior institutionalization (e.g. Did this patient come from a nursing home prior to being admitted?)
For future presentations, can explain the terminology more clearly, to describe and differentiate between 'colonization' and 'infection'.
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