Healthcare Facility-Associated Clostridium difficile Infection in Hospitalized Patients Receiving Intravenous Beta-Lactam Antibiotics in the Veterans Affairs Healthcare System Brigid M. Wilson PhD 1 , Federico Perez MD 1,2,3 , Elie Saade MD 2 and Curtis J. Donskey MD 1,3 1 Geriatric Research, Education and Clinical Center, Cleveland VA Medical Center; 2 Department of Medicine, University Hospitals Cleveland Medical Center, 3 Infectious Diseases Section, Cleveland VA Medical Center Background • Antibiotic exposure in the intestinal tract is the most important risk factor for Clostridium difficile infection (CDI) • Oral administration of beta-lactamase enzymes such as SYN-004 (Synthetic Biologics, Inc) has been effective in eliminating the portion of intravenous beta-lactam antibiotics excreted into the intestinal tract, preserving the microbiota during therapy • We examined patterns of use of beta-lactams and the relative frequency of healthcare facility- associated (HCFA)-CDI associated with them given alone or combined with other antibiotics • Using nationwide databases, we identified systemic antibiotics administered for hospitalizations in the VHA from 2006-2015 • We identified CDI based on toxin/PCR/EIA test • Rates of HCFA-CDI (cases per hospitalization) calculated for any antibiotic treatment and by selected beta-lactam and fluoroquinolone (FLQ) agents • Additional risk factors for CDI assessed Methods Conclusions • The beta-lactam antibiotics studied were prescribed in nearly a third of analyzed hospitalizations and were frequently associated with HCFA-CDI (>5,000 cases/year) • Receipt of multiple antibiotics and non- antimicrobial factors may increase the risk for CDI in antibiotic-treated patients • Interventions such as SYN-004 that prevent beta- lactam-induced disruption of the intestinal microbiota could reduce HCFA-CDI Funding Results Antibiotics N(%) hospitalizations % CDI within 48 hours of admission % CDI > 48 after admission <28 days after discharge None 541893 (50%) 0.0% 0.1% Antibiotics of interest 418050 (39%) 0.4% 1.3% Other antibiotics 116221 (11%) 1.2% 0.9% Table 1. Percentage of hospitalizations associated with CDI, by antibiotic exposure Table 2. Bivariate and multivariate analysis of risk factors for HCFA-CDI Risk factor Bivariate OR (95% CI) Multivariate OR (95% CI) Any antibiotics 8.7 (8.07, 9.37) 4.72 (4.36, 5.12) Female 0.75 (0.67, 0.84) 1.11 (0.98, 1.25) ICU 1.57 (1.46, 1.69) 1.04 (0.97, 1.13) Prior outpatient antibiotics 1.1 (1.03, 1.17) 1.03 (0.97, 1.1) Nursing home 4.11 (3.9, 4.34) 1.76 (1.66, 1.87) Braden scale < 19 4.95 (4.68, 5.24) 1.79 (1.68, 1.9) Charlson > 4 1.63 (1.56, 1.71) 1.22 (1.16, 1.28) Length of stay > 4 days 7.32 (6.91, 7.77) 2.95 (2.76, 3.16) Age 75+ 1.55 (1.48, 1.63) 1.02 (0.96, 1.07) Surgical admission 0.82 (0.77, 0.86) 0.79 (0.75, 0.84) Creatinine > 1 1.49 (1.42, 1.56) 1.2 (1.14, 1.26) Albumin > 3.5 0.21 (0.2, 0.23) 0.45 (0.42, 0.48) Acid suppressants 2.3 (2.18, 2.42) 1.43 (1.35, 1.51) Figure 1. CDI in hospitalized patients receiving therapy with selected antibiotics Corresponding Author: [email protected] Figure 2. CDI in patients receiving selected antibiotics alone or in conjunction with other agents Figure 3. CDI by # of antibiotics and Braden score Figure 4. CDI in ceftriaxone-treated patients with or without additional risk factors A. Ceftriaxone B. Piperacillin/tazobactam (PipTazo) NOTES: Braden scale is a tool for assessing pressure ulcer risk where scores <19 indicate increased risk; Charlson comorbidity index calculated from inpatient and outpatient ICD9 codes; univariate odds ratios generated using Mantel-Hanzel method; lab measures as the first after admission; multivariate odds ratios from a logistic model estimated in SAS 9.2 on hospitalizations with complete data. 2067

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Page 1: 2067 Healthcare Facility-Associated Clostridium …content.stockpr.com/syntheticbiologics/db/220/748/file/...Healthcare Facility-Associated Clostridium difficile Infection in Hospitalized

Healthcare Facility-Associated Clostridium difficile Infection in Hospitalized Patients Receiving Intravenous Beta-Lactam

Antibiotics in the Veterans Affairs Healthcare SystemBrigid M. Wilson PhD1, Federico Perez MD1,2,3, Elie Saade MD2 and Curtis J. Donskey MD1,3

1Geriatric Research, Education and Clinical Center, Cleveland VA Medical Center; 2Department of Medicine, University Hospitals Cleveland Medical Center, 3Infectious Diseases Section, Cleveland VA Medical Center

Background• Antibioticexposureintheintestinaltractisthe

mostimportantriskfactorforClostridiumdifficile infection(CDI)

• Oraladministrationofbeta-lactamaseenzymessuchasSYN-004(SyntheticBiologics,Inc)hasbeeneffectiveineliminatingtheportionofintravenousbeta-lactamantibioticsexcretedintotheintestinaltract,preservingthemicrobiotaduringtherapy

• Weexaminedpatternsofuseofbeta-lactamsandtherelativefrequencyofhealthcarefacility-associated(HCFA)-CDIassociatedwiththemgivenaloneorcombinedwithotherantibiotics

• Usingnationwidedatabases,weidentifiedsystemicantibioticsadministeredforhospitalizationsintheVHAfrom2006-2015

• WeidentifiedCDIbasedontoxin/PCR/EIAtest• RatesofHCFA-CDI(casesperhospitalization)

calculatedforanyantibiotictreatmentandbyselectedbeta-lactamandfluoroquinolone(FLQ)agents

• AdditionalriskfactorsforCDIassessed

Methods

Conclusions• The beta-lactam antibiotics studied were prescribed

in nearly a third of analyzed hospitalizations andwere frequently associated with HCFA-CDI (>5,000cases/year)

• Receipt of multiple antibiotics and non-antimicrobial factors may increase the risk for CDI inantibiotic-treated patients

• Interventions such as SYN-004 that prevent beta-lactam-induced disruption of the intestinalmicrobiota could reduce HCFA-CDI

Funding

Results

Antibiotics N(%)hospitalizations %CDI within48hoursofadmission

%CDI >48afteradmission<28daysafterdischarge

None 541893(50%) 0.0% 0.1%Antibioticsofinterest 418050(39%) 0.4% 1.3%Otherantibiotics 116221(11%) 1.2% 0.9%

Table1.PercentageofhospitalizationsassociatedwithCDI,byantibioticexposureTable2.BivariateandmultivariateanalysisofriskfactorsforHCFA-CDI

Riskfactor BivariateOR(95%CI)

MultivariateOR(95%CI)

Anyantibiotics 8.7(8.07,9.37) 4.72(4.36,5.12)

Female 0.75(0.67,0.84) 1.11(0.98,1.25)

ICU 1.57(1.46,1.69) 1.04(0.97,1.13)

Prioroutpatientantibiotics 1.1(1.03,1.17) 1.03(0.97,1.1)

Nursinghome 4.11(3.9,4.34) 1.76(1.66,1.87)

Bradenscale<19 4.95(4.68,5.24) 1.79(1.68,1.9)

Charlson >4 1.63(1.56,1.71) 1.22(1.16,1.28)

Lengthofstay>4days 7.32(6.91,7.77) 2.95(2.76,3.16)

Age75+ 1.55(1.48,1.63) 1.02(0.96,1.07)

Surgicaladmission 0.82(0.77,0.86) 0.79(0.75,0.84)

Creatinine>1 1.49(1.42,1.56) 1.2(1.14,1.26)

Albumin>3.5 0.21(0.2,0.23) 0.45(0.42,0.48)

Acidsuppressants 2.3(2.18,2.42) 1.43(1.35,1.51)

Figure1.CDIinhospitalizedpatientsreceivingtherapywithselectedantibiotics

Corresponding Author: [email protected]

Figure2.CDIinpatientsreceivingselectedantibioticsaloneorinconjunctionwithotheragents

Figure3.CDIby#ofantibioticsandBradenscore Figure4.CDIinceftriaxone-treatedpatientswithorwithoutadditionalriskfactors

A.Ceftriaxone B.Piperacillin/tazobactam (PipTazo)

NOTES: Braden scale is a tool for assessing pressure ulcer risk where scores <19indicate increased risk; Charlson comorbidity index calculated from inpatient andoutpatient ICD9 codes; univariate odds ratios generated using Mantel-Hanzelmethod; lab measures as the first after admission; multivariate odds ratios from alogistic model estimated in SAS 9.2 on hospitalizations with complete data.

2067