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Supplemental MaterialEnrollment criteriaPatients were included if they were adults (age >18 years), had a urine and/or blood culture positive for at least one gram-negative organism obtained at any time during hospitalization, and underwent antibiotic treatment on the day index culture was drawn, which continued for >3 consecutive days. To identify cUTI patients we developed an ICD-9-CM based algorithm, which is available in Table 1.Patients were excluded if they were <18 years, had a hospital LOS <2 days, were transferred from another acute care facility, or if the cUTI episode was a repeat bout during the index hospitalization (as evidenced by a >3-day hiatus in UTI-specific antimicrobial regimen administration and a new positive culture). In order to increase the likelihood that the identified gram-negative organism originated in the urine rather than another site, we excluded all patients who fit the definition for complicated intra-abdominal infection (Table 2).Microbiology and treatment variables and definitionsIn addition to growing at least one gram-negative organism for inclusion in the cohort, a patient has to grow out a qualifying organism in the urine and/or blood in order to be considered culture-positive. Gram-negative organisms of particular interest were: Pseudomonas aeruginosa, Acinetobacter bamannii, Stenotrophomonas maltophilia (assumed always to be CR), and Enterobacteriaceae, as listed in Table anisms were classified as carbapenem S (susceptible), I (intermediate) or R (resistant). For the purposes of the current analyses, I and R were grouped together as resistant. CR was defined as any organism with an I or R in the susceptibility category to one of the four carbapenems – imipenem, meropenem, ertapenem or doripenem. CS was defined as any organism with a S in the susceptibility category to either any carbapenem tested or to any third generation cephalosporin (Table 4) tested. First detection of a CR organism served as the index culture; if there was no CR organism detected, then the first culture growing out one of the organisms of interest served as the index culture. Table 1. Selection algorithm for complicated urinary tract infection (cUTI, catheter-associated UTI [CAUTI] analyzed as a subgroup of cUTI)AlgorithmCAUTI = Any Group A OR (At least one group B + At least one group C)cUTI = (At least one group B + At least one group D) OR (At least one group B + At least one group E) CodeDescriptionGroup A996.64Infection and inflammatory reaction due to indwelling urinary catheterGroup BPyelonephritis590.1xAcute pyelonephritis590.0xChronic pyelonephritis590.8Unspecified pyelonephritis590.3Pyeloureteritis cysticaGroup CUrinary Catheter57.94Insertion of indwelling urinary catheter57.95Replacement of indwelling urinary catheter96.48Irrigation of indwelling urinary catheterV53.6Urinary catheterV55.6Attention to other artificial opening of urinary tractGroup DUrinary Tract Obstruction or other abnormality593.7xVesicoureteral reflux592.xNephrolithiasis or ureteric calculi753.2xObstructive defect of renal pelvis and ureter599.6xUrinary obstruction600.xProstate hyperplasia596.0Bladder neck obstruction591Hydronephrosis788.2xRetention of urineGroup EImmunocompromisedV 58.1Encounter for chemotherapy and immunotherapy for neoplastic conditionsV 15.3 Personal history of irradiationV 42Organ or tissue replaced by transplantReceived ≥ 5mg prednisone equivalentTable 2. cIAI identification algorithm*cIAI = at least 1 diagnosis code + at least 1 procedure codeCodeDiagnosis531.1X, 531.5XGastric ulcer with perforation531.2X, 531.6XGastric ulcer with hemorrhage and perforation532.1X, 532.5XDuodenal ulcer with perforation532.2X, 532.6XDuodenal ulcer with hemorrhage and perforation533.1X, 533.5XPeptic ulcer with perforation533.2X, 533.6XPeptic ulcer with hemorrhage and perforation534.1X, 534.5XGastrojejunal ulcer with perforation534.2X, 534.6XGastrojejunal ulcer with hemorrhage and perforation540.0Acute appendicitis with generalized peritonitis540.1Acute appendicitis with peritoneal abscess567.XPeritonitis569.5Abscess of intestine569.81Fistula of intestine, excl. rectum and anus569.82Ulceration of intestine569.83Perforation of intestine572.0Abscess of liver575.4 plus 574.0, 574.3, 574.6, 574.8, or 575.0Acute cholecystitisCodeProcedure43.5X-43.9X Laparotomy/laparoscopy 44.40-44.42?44.61?45.6X-46.13?46.20-46.23?46.7X?46.80-46.82?46.91-46.94?46.99? 47.XX?50.0X?50.12-50.69?51.02-51.04?51.13?51.2X?51.3X?51.4X-51.5X?51.61-51.63?51.61-51.63?51.61-51.63?51.61-51.63?51.61-51.63?51.61-51.63?51.61-51.63?51.61-51.63?51.69?51.7X? 51.81-51.83?51.89? 51.91-51.95?51.99?52.01?52.09?52.12?52.22?52.3X-52.83?52.92?52.95?52.96?52.99?54.1X?54.21?54.4X?54.5X?54.92-54.95?*In ICD-9-CM, "X" denotes a wildcard that includes a missing digit as well as the range of digits that span from 0 to 9 (Reference #18 and personal communication with G. Oster re: laparotomy/laparoscopy codes)Table 3. Enterobacteriaceae included in the analysisE. coliProteus spp.K. pneumoniaeS. marcesens K. oxytocaC. freundiiE. cloacaeM. morganiiE. aerogenesProvidencia spp.P. mirabilisTable 4. Third generation cephalosporinsCeftibutenCefiximeCeftriaxoneCefditorenCefotaximeCeftizoximeCefpodoximeCefoperazoneCefdinirCeftazidimeTable 5. Baseline characteristics?CR (N = 1,357)CS (N = 23,928 )?N%N%P-valueMean age, years (SD)64.1 (17.9)?64.0 (18.7)?0.86Gender: male85563.01%10,52643.99%<0.001Race?????White 96671.19%17,26072.13%0.011Black24518.05%3,57614.94%Hispanic161.18%3231.35%Other1279.36%2,71311.34%Unknown30.22%560.23%Admission Source?????Non-healthcare facility (including from home)96270.89%17,28472.23%<0.001Clinic473.46%9323.90%Transfer from ECF17913.19%1,8297.64%Transfer from another non-acute care facility00.00%30.01%Emergency Department13910.24%3,15213.17%Other302.21%7283.04%Admission type?????Medical1,16085.48%20,46985.54%0.950Surgical19714.52%3,45914.46%?Neurologic372.73%6692.80%0.880Trauma382.80%7663.20%0.413Elixhauser Comorbidities?????Congestive heart failure24417.98%3,64615.24%0.006Valvular disease674.94%1,3025.44%0.425Pulmonary circulation disease402.95%6462.70%0.584Peripheral vascular disease14210.46%1,7597.35%<0.001Paralysis45533.53%3,79615.86%<0.001Other neurological disorders33824.91%4,48518.74%<0.001Chronic pulmonary disease28821.22%4,97320.78%0.698Diabetes without chronic complications49536.48%8,48435.46%0.444Diabetes with chronic complications1138.33%2,2219.28%0.237Hypothyroidism22016.21%3,66815.33%0.380Renal failure37227.41%5,60023.40%0.001Liver disease463.39%7883.29%0.846Peptic ulcer disease with bleeding10.07%320.13%1.000AIDS30.22%320.13%0.434Lymphoma241.77%1730.72%<0.001Metastatic cancer473.46%6652.78%0.138Solid tumor without metastasis463.39%7132.98%0.389Rheumatoid arthritis/collagen vascular594.35%1,0724.48%0.819Coagulopathy886.48%1,9728.24%0.021Obesity20014.74%3,85716.12%0.178Weight loss24618.13%2,51210.50%<0.001Fluid and electrolyte disorders60444.51%10,68144.64%0.926Chronic blood loss anemia251.84%3991.67%0.626Deficiency anemia54540.16%8,00933.47%<0.001Alcohol abuse231.69%4812.01%0.419Drug abuse584.27%6462.70%0.001Psychosis705.16%1,2545.24%0.895Depression28921.30%3,86216.14%<0.001Hypertension63146.50%11,88749.68%0.023Charlson Comoribidity Score?????015111.13%5,48422.92%<0.001118413.56%4,26617.83%233324.54%4,95720.72%325418.72%3,47414.52%417913.19%2,41610.10%5+25618.87%3,33113.92%Mean (SD)2.9 (2.2)?2.3 (2.2)??Median [IQR]3 [2,4]?2 [1,3]??Hospital Characteristics?????Census region?????Midwest35025.79%5,88424.59%0.004Northeast20915.40%3,93416.44%South52538.69%10,08142.13%West27320.12%4,02916.84%Number of Beds?????<100413.02%7122.98%<0.001100 to 1991339.80%3,09212.92%200 to 29935626.23%5,23321.87%300 to 39918513.63%4,25517.78%400 to 49921315.70%3,38514.15%500+42931.61%7,25130.30%Teaching59143.55%10,81345.19%0.238Urban1,24891.97%21,62490.37%0.052CR Rate at Hospital Level?????Mean (SD)4.7% (4.2)????Median [IQR]4.0% [1.6%, 6.6%]????CR = carbapenem resistant; CS = carbapenem susceptible; SD = standard deviation; ECF = extended care facility; AIDS = acquired immune deficiency syndrome; IQR = interquartile range Table 6. Hospitalization eventsCR (N = 1,357)CS (N = 23,928 )N%N%P-valueInfection subtype ?????cUTI32624.02%12,73053.20%<0.001CAUTI103175.98%11,19846.80%Risk factors for CRHospital Onset (HO)1067.81%1,7107.15%?Community Onset (CO)1,25192.19%22,21892.85%0.356Community Acquired CO (CA-CO)43932.35%10,97645.87%?Health Care Associated CO (HCA-CO)81259.84%11,24246.98%<0.001Antibiotics within 90 days prior to admission68250.26%6,24726.11%<0.001CR organism within 90 days prior to admission16011.79%2160.90%<0.001Time to infection onset from admission, days?????cUTI?????Mean (SD)1.6 (2.5)?1.2 (2.0)?0.001Median [IQR]1 [1,1]?1 [1,1]?0.003CAUTI?????Mean (SD)1.8 (4.4)?2.0 (3.6)?0.049Median [IQR]1 [1,1]?1 [1,1]?0.130Illness severity at infection onset ?????ICU admission28921.30%4,88720.42%0.438Mechanical ventilation1188.70%1,3255.54%<0.001Vasopressors674.94%1,8057.54%<0.001Dialysis443.24%5312.22%0.014Severe sepsis25118.50%4,41618.46%0.970Septic shock14410.61%2,60210.87%0.762Mean (SD) time to cUTI treatment, days1.1 (0.5)?1.2 (1.2)?<0.001CR = carbapenem resistant; CS = carbapenem susceptible; cUTI = complicated urinary tract infection; CAUTI = cathater-associated urinary tract infection; HO = hospital-onset; CO = community-onset; CA = community-acquired; HCA = healthcare associated; SD = standard deviation; IQR = interquartile range; ICU = intensive care unit; Table 7. Microbiology and empiric treatmentCR (N = 1,357)CS (N = 23,928 )N%N%P-valuecUTI organism ?????Klebsiella pneumoniae23217.10%3,49914.62%0.012Proteus mirabilis17913.19%3,18613.31%0.896Escherichia coli15611.50%13,55956.67%<0.001Enterobacter cloacae352.58%6432.69%0.811Providencia spp483.54%5352.24%0.002Serratia marcescens211.55%3371.41%0.673Morganella morganii594.35%4521.89%<0.001Enterobacter aerogenes161.18%2891.21%0.925Proteus spp.18713.78%3,29213.76%0.981Citrobacter freundii201.47%4351.82%0.354Klebsiella oxytoca 130.96%4751.99%0.007Enterobacter other211.55%3271.37%0.578Citrobacter other120.88%2571.07%0.507Serratia other30.22%310.13%0.428Klebsiella other40.29%610.25%0.779Pseudomonas aeruginosa74054.53%3,21613.44%<0.001Acinetobacter baumannii775.67%1290.54%<0.001Stenotrophomonas maltophilia16812.38%00.00%<0.001Empiric antibiotics?????Antipseudomonal penicillins with beta-lactamase inhibitor46334.12%7,18830.04%0.001Extended spectrum cephalosporins65848.49%13,74657.45%<0.001Antipseudomonal floroquinolones45933.82%10,06742.07%<0.001Antipseudomonal carbapenems25718.94%3,05112.75%0.186Aminoglycosides18013.26%2,41110.08%<0.001Penicillins with beta-lactamase inhibitors251.84%4051.69%0.678Tetracyclines241.77%2491.04%0.012Folate pathway inhibitors402.95%6192.59%0.417Polymyxins50.37%290.12%0.016Antipseudomonal cephalosporins33024.32%3,62015.13%<0.001Aztreonam624.57%9003.76%0.130Fosfomycin40.29%280.12%0.073Tigecycline543.98%1930.81%<0.0013rd generation cephalosporin48335.59%12,18750.93%<0.001Empiric treatment appropriateness?????Non-IET51537.95%17,91874.88%<0.001IET46734.41%2,68811.23%Indeterminate37527.63%3,32213.88%CR = carbapenem resistant; CS = carbapenem susceptible; cUTI = complicated urinary tract infection; IET = inappropriate empiric therapy ................
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