Appendix Table 1. Dosage form codes for oral and injected drugs. Appendix Table 3. Number of beneficiaries meeting each inclusion criterion.

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Appendix Olesen SW, Barnett ML, MacFadden DR, et al. Trends in outpatient antibiotic prescribing practice among US older adults, 2011-2015: an observational study. Appendix Table 1. Dosage form codes for oral and injected drugs. Appendix Table 2. Antibiotic generic names. Appendix Table 3. Number of beneficiaries meeting each inclusion criterion. Appendix Table 4. Trends in study population characteristics. Appendix Table 5. Patterns and trends in overall antibiotic use by demography and geography. Appendix Table 6. Trends in use of azithromycin, levofloxacin, and amoxicillin/clavulanate for respiratory conditions, linking each claim with only one diagnosis. Appendix Table 7. Trends in use of ciprofloxacin, metronidazole, and levofloxacin for gastrointestinal conditions. Appendix Table 8. Trends in use of ciprofloxacin, nitrofurantoin, and trimethoprim/sulfamethoxazole for genitourinary conditions. Appendix Table 9. Trends in use of cephalexin, trimethoprim/sulfamethoxazole, and ciprofloxacin for skin, cutaneous, and mucosal conditions. 1

Appendix Table 1. Dosage form codes for oral and injected drugs. Part D Events were filtered for oral and injected drugs using the values in this table. Dosage code Dosage form CA CAPSULE CE CAPSULE,DELAYED RELEASE (ENTERIC COATED) CJ CAPSULE,EXTENDED RELEASE MULTIPHASE 24HR HH AMPUL (ML) HK IV SOLUTION, PIGGYBACK PREMIX FROZEN(ML) HM INTRAVENOUS SOLUTION HP INTRAVENOUS SOLUTION, PIGGYBACK (ML) HQ DISPOSABLE SYRINGE (ML) HQ SYRINGE (ML) HS VIAL (SDV,MDV OR ADDITIVE) (EA) HS VIAL (EA) HV VIAL (SDV,MDV OR ADDITIVE) (ML) HV VIAL (ML) IF VIAL WITH THREADED PORT (EA) IG VIAL WITH THREADED PORT (ML) IM CAPSULE,IMMEDIATE, DELAY RELEASE,BIPHASE PD SUSPENSION, RECONSTITUTED, ORAL (ML) PI SOLUTION, RECONSTITUTED, ORAL PP PACKET (EA) QI SUSPENSION, EXTENDED RELEASE, RECONST. RG SUSPENSION, MICROCAPSULE RECONSTITUTED RH DROPS, VISCOUS (ML) SC SUSPENSION, ORAL (FINAL DOSE FORM) SJ SOLUTION, ORAL ST SYRUP TA TABLET TC TABLET, CHEWABLE TE TABLET, DELAYED RELEASE (ENTERIC COATED) TM TABLET, EXTENDED RELEASE 12 HR TS TABLET, EXTENDED RELEASE UP TABLET,EXTENDED RELEASE MULTIPHASE 24 HR ZD COMBINATION PACKAGE (EA) 2

Appendix Table 2. Antibiotic generic names. Part D Events were filtered for antibiotics using the generic names in this table. Generic name Antibiotic AMIKACIN SULFATE amikacin AMOXICILLIN amoxicillin AMOXICILLIN/POTASSIUM CLAV amoxicillin/clavulanate AMPICILLIN SODIUM ampicillin AMPICILLIN SODIUM/SULBACTAM NA ampicillin AMPICILLIN TRIHYDRATE ampicillin AZITHROMYCIN azithromycin AZTREONAM aztreonam AZTREONAM LYSINE aztreonam AZTREONAM/DEXTROSE-WATER aztreonam BACITRACIN bacitracin BACITRACIN/POLYMYXIN B SULFATE bacitracin BEDAQUILINE FUMARATE bedaquiline BESIFLOXACIN HCL besifloxacin BESIFLOXACIN HYDROCHLORIDE besifloxacin BISMUTH SAL/METRONID/TETRACYC metronidazole/tetracycline BISMUTH/METRONID/TETRACYCLINE metronidazole/tetracycline CAPREOMYCIN SULFATE capreomycin CEFACLOR cefaclor CEFADROXIL cefadroxil CEFADROXIL HYDRATE cefadroxil CEFAZOLIN SODIUM cefazolin CEFAZOLIN SODIUM/DEXTROSE,ISO cefazolin CEFDINIR cefdinir CEFDITOREN PIVOXIL cefditoren CEFEPIME HCL cefepime CEFIXIME cefixime CEFOTAXIME SODIUM cefotaxime CEFOTETAN DISODIUM cefotetan CEFOXITIN SODIUM cefoxitin CEFOXITIN SODIUM/DEXTROSE,ISO cefoxitin CEFPODOXIME PROXETIL cefpodoxime CEFPROZIL cefprozil CEFTAROLINE FOSAMIL ACETATE ceftaroline CEFTAZIDIME ceftazidime CEFTAZIDIME IN DEXTROSE5%WATER ceftazidime CEFTAZIDIME NA/DEXTROSE,ISO ceftazidime CEFTAZIDIME PENTAHYDRATE ceftazidime CEFTAZIDIME PENTAHYDRATE/D5W ceftazidime CEFTIBUTEN DIHYDRATE ceftibuten CEFTRIAXONE SODIUM ceftriaxone CEFUROXIME AXETIL cefuroxime 3

CEFUROXIME SODIUM CEFUROXIME SODIUM/DEXTROSE,ISO CEFUROXIME SODIUM/WATER CEPHALEXIN CHLORAMPHENICOL NA SUCC CHLORAMPHENICOL SOD SUCC CHLORHEXIDINE GLUCONATE CIPROFLOXACIN CIPROFLOXACIN HCL CIPROFLOXACIN HCL/DEXAMETH CIPROFLOXACIN LACTATE CIPROFLOXACIN LACTATE/D5W CIPROFLOXACIN/CIPROFLOXA HCL CIPROFLOXACIN/HYDROCORTISONE CLARITHROMYCIN CLINDAMYCIN HCL CLINDAMYCIN PALMITATE HCL CLINDAMYCIN PHOS/BENZOYL PEROX CLINDAMYCIN PHOS/SKIN CLNSR 19 CLINDAMYCIN PHOSPHATE CLINDAMYCIN PHOSPHATE/D5W CLINDAMYCIN/BENZ PER/HYALUR NA CLINDAMYCIN/TRETINOIN COLISTIN (COLISTIMETHATE NA) CYCLOSERINE DAPTOMYCIN DEMECLOCYCLINE HCL DICLOXACILLIN SODIUM DORIPENEM DOXYCYCLINE CALCIUM DOXYCYCLINE HYCLATE DOXYCYCLINE MONOHYDRATE ERTAPENEM SODIUM ERY E-SUCC/SULFISOXAZOLE ERYTHROMYCIN BASE ERYTHROMYCIN BASE/ETHANOL ERYTHROMYCIN ETHYLSUCCINATE ERYTHROMYCIN LACTOBIONATE ERYTHROMYCIN STEARATE ERYTHROMYCIN/BENZOYL PEROXIDE ETHAMBUTOL HCL ETHIONAMIDE FIDAXOMICIN FOSFOMYCIN TROMETHAMINE GATIFLOXACIN cefuroxime cefuroxime cefuroxime cephalexin chloramphenicol chloramphenicol chlorhexidine ciprofloxacin ciprofloxacin ciprofloxacin ciprofloxacin ciprofloxacin ciprofloxacin ciprofloxacin clarithromycin colistin cycloserine daptomycin demeclocycline dicloxacillin doripenem doxycycline doxycycline doxycycline ertapenem erythromycin/sulfisoxazole erythromycin erythromycin erythromycin erythromycin erythromycin erythromycin ethambutol ethionamide fidaxomicin fosfomycin gatifloxacin 4

GEMIFLOXACIN MESYLATE gemifloxacin GENTAMICIN IN NACL, ISO-OSM gentamicin GENTAMICIN SULFATE gentamicin GENTAMICIN SULFATE/PF gentamicin GENTAMICIN/PREDNISOL AC gentamicin IMIPENEM/CILASTATIN SODIUM imipenem ISONIAZID isoniazid KANAMYCIN SULFATE kanamycin LANSOPRAZOLE/AMOXICILN/CLARITH clarithromycin/amoxicillin LEVOFLOXACIN levofloxacin LEVOFLOXACIN/D5W levofloxacin LEVOFLOXACIN/DEXTROSE 5%-WATER levofloxacin LINCOMYCIN HCL lincomycin LINEZOLID linezolid MEROPENEM meropenem METRONIDAZOLE metronidazole METRONIDAZOLE/SODIUM CHLORIDE metronidazole MINOCYCLINE HCL minocycline MINOCYCLINE HCL/SKIN CL NO.4 minocycline MOXIFLOXACIN HCL moxifloxacin MOXIFLOXACIN IN NACL (ISO-OSM) moxifloxacin NAFCILLIN IN DEXTROSE,ISO-OSM nafcillin NAFCILLIN SODIUM nafcillin NAFCILLIN SODIUM/D2.4W nafcillin NEO/POLYMYX B SULF/DEXAMETH neomycin/polymyxin B NEOMY SULF/BACITRA/POLYMYXIN B neomycin/bacitracin/polymyxin B NEOMY SULF/BACITRAC ZN/POLY/HC neomycin/bacitracin/polymyxin B NEOMY SULF/COLIST SUL/HC/THONZ neomycin/colistin NEOMY SULF/POLYMYX B SULF/PRED neomycin/polymyxin B NEOMY SULF/POLYMYXIN B SULFATE neomycin/polymyxin B NEOMYCIN SULFATE neomycin NEOMYCIN SULFATE/FLUOCINOLONE neomycin NEOMYCIN/BACITRA/POLYMYXIN/HC neomycin/bacitracin/polymyxin B NEOMYCIN/POLYMYXIN B SULF/HC neomycin/polymyxin B NEOMYCIN/POLYMYXN B/GRAMICIDIN neomycin/polymyxin B NITROFURANTOIN nitrofurantoin NITROFURANTOIN MACROCRYSTAL nitrofurantoin NITROFURANTOIN MONOHYD/M-CRYST nitrofurantoin NORFLOXACIN norfloxacin OFLOXACIN ofloxacin OMEPRAZOLE/CLARITH/AMOXICILLIN clarithromycin/amoxicillin OXACILLIN SODIUM oxacillin OXACILLIN SODIUM/DEXTROSE,ISO oxacillin PAROMOMYCIN SULFATE paromomycin PEN G BENZ/PEN G PROCAINE penicillin G 5

PEN G POT/DEXTROSE-WATER PENICILLIN G BENZATHINE PENICILLIN G POTASSIUM PENICILLIN G PROCAINE PENICILLIN G SODIUM PENICILLIN V POTASSIUM PIPERACILLIN SODIUM PIPERACILLIN SODIUM/TAZOBACTAM PIPERACILLIN-TAZO-DEXTROSE,ISO POLYMYXIN B SULF/TRIMETHOPRIM POLYMYXIN B SULFATE POLYMYXIN B SULFATE/TMP PYRAZINAMIDE QUINUPRISTIN/DALFOPRISTIN RETAPAMULIN RIFABUTIN RIFAMP/ISONIAZID/PYRAZINAMIDE RIFAMPIN RIFAMPIN/ISONIAZID RIFAMPIN/ISONIAZID/PYRAZINAMID RIFAPENTINE RIFAXIMIN STREPTOMYCIN SULFATE SULFACETAMIDE SODIUM SULFACETAMIDE/PREDNISOLONE SP SULFACETM NA/PREDNISOL AC SULFADIAZINE SULFAMETHOXAZOLE/TRIMETHOPRIM TEDIZOLID PHOSPHATE TELAVANCIN HCL TELITHROMYCIN TETRACYCLINE HCL TICARCILLIN/K CLAVULANATE TIGECYCLINE TINIDAZOLE TOBRAMYCIN TOBRAMYCIN IN 0.225% NACL TOBRAMYCIN SULF/DEXAMETHASONE TOBRAMYCIN SULFATE TOBRAMYCIN/DEXAMETHASONE TOBRAMYCIN/LOTEPRED ETAB TOBRAMYCIN/SODIUM CHLORIDE TRIMETHOPRIM VANCOMYCIN HCL penicillin G penicillin G penicillin G penicillin G penicillin G penicillin V piperacillin piperacillin/tazobactam piperacillin/tazobactam polymyxin B/trimethoprim polymyxin B polymyxin B/trimethoprim pyrazinamide quinupristin/dalfopristin retapamulin rifabutin rifampin/isoniazid/pyrazinamide rifampin rifampin/isoniazid rifampin/isoniazid/pyrazinamide rifapentine rifaximin streptomycin sulfacetamide sulfacetamide sulfacetamide sulfadiazine trimethoprim/sulfamethoxazole tedizolid telavancin telithromycin tetracycline ticarcillin/clavulanate tigecycline tinidazole tobramycin tobramycin tobramycin tobramycin tobramycin tobramycin tobramycin trimethoprim vancomycin 6

Appendix Table 3. Number of beneficiaries meeting each inclusion criterion. Increase in size of the study population (bottom row) is due to an increase in the size of the overall Medicare population (top row), increasing age of the Medicare population, and increasing number of beneficiaries of full-year coverage for Parts A, B, and D. No. eligible beneficiaries (% retained from previous step) Criterion 2011 2012 2013 2014 2015 20% sample a 10,341,350 (ref) 10,707,986 (ref) 11,053,790 (ref) 11,550,386 (ref) 12,365,119 (ref) Age 65 7,998,700 (77.3) 8,251,542 (77.1) 8,577,277 (77.6) 9,030,236 (78.2) 9,777,278 (79.1) Parts A, B, D b 2,435,965 (30.5) 2,581,773 (31.3) 2,997,160 (34.9) 3,144,145 (34.8) 3,431,090 (35.1) Demographic data c 2,429,554 (99.7) 2,575,367 (99.8) 2,990,851 (99.8) 3,136,990 (99.8) 3,425,194 (99.8) a: Beneficiaries in the 20% sample provided by Medicare b: 12 months of eligibility for all three Parts c: Sex is coded as male or female, and state of residence code matches one of the 50 states or District of Columbia 7

Appendix Table 4. Trends in study population characteristics. Population characteristic trend*, % (95% CI) Age (%) 65-74 5.01 (4.85 to 5.17) 75-84 5.14 ( 5.33 to 4.94) 85-94 4.04 ( 4.37 to 3.71) 95 0.81 ( 0.33 to 1.97) Mean no. chronic conditions 0.038 ( 0.127 to 0.050) % female 1.10 ( 1.21 to 0.98) % white 2.68 (2.61 to 2.75) % dual eligible for Medicaid 34.5 ( 34.6 to 34.3) Region % South 1.94 ( 2.12 to 1.75) % Midwest 2.98 ( 3.23 to 2.72) % West 0.35 ( 0.66 to 0.03) % Northeast 8.19 (7.87 to 8.52) *: 2011-2015 change from Poisson regression (for first 3 characteristics) or log-binomial regression (for proportions) on population characteristic. 8

Appendix Table 5. Patterns and trends in overall antibiotic use by demography and geography. Claims per 1,000 beneficiaries per year 2011 2015 change*, % (95% CI) Overall 1365 1364 0.20 ( 0.30 to 0.09) Age 65-74 1296 1277 1.05 ( 1.23 to 0.86) 75-84 1386 1410 1.05 (0.83 to 1.26) 85-94 1498 1519 0.02 ( 0.33 to 0.28) 95 1622 1608 3.3 ( 4.2 to 2.5) Sex female 1469 1475 0.78 (0.62 to 0.93) male 1187 1179 2.4 ( 2.6 to 2.2) Race white 1407 1416 0.42 (0.28 to 0.56) Hispanic 1275 1224 2.8 ( 3.3 to 2.2) other 1230 1106 5.5 ( 6.1 to 4.9) black 1074 1023 3.6 ( 4.1 to 3.0) Region South 1487 1519 0.80 (0.60 to 0.99) Midwest 1351 1335 1.5 ( 1.8 to 1.3) West 1266 1203 4.4 ( 4.7 to 4.1) Northeast 1218 1246 2.9 (2.6 to 3.2) *: Adjusted value for 2011-2015 change from Poisson regression on claims per beneficiary per year adjusted for dual eligibility, number of chronic conditions, and (depending on subpopulation) age, sex, race, and US Census region. 9

Appendix Table 6. Trends in use of azithromycin, levofloxacin, and amoxicillin/clavulanate for respiratory conditions, linking each claim with only one diagnosis. Diagnosis Antibiotics appropriate? b Claims per 1,000 beneficiaries per year a Azithromycin Levofloxacin Amoxicillin/clavulanate 2011 2014 change c (%) 2011 2014 change c (%) 2011 2014 change c (%) Pneumonia d Yes 5.9 4.7 17.1 ± 1.9 7.8 10.0 30.9 ± 2.2 2.2 2.1 0.4 ± 3.5 Sinusitis Potentially 21.9 17.7 22.7 ± 0.9 4.1 7.7 69.1 ± 3.5 11.3 15.6 35.9 ± 2.0 VURI e No 39.6 34.0 14.2 ± 0.8 9.2 13.9 52.8 ± 2.3 6.2 8.0 32.0 ± 2.6 Acute bronchitis f No 38.2 29.3 23.0 ± 0.7 8.2 12.6 49.1 ± 2.3 5.2 5.8 13.3 ± 2.5 Other respiratory g No 29.2 23.6 16.5 ± 0.9 20.6 25.7 30.1 ± 1.4 9.9 10.3 9.4 ± 1.8 Asthma & allergy h No 11.0 9.4 15.1 ± 1.4 3.2 4.7 44.0 ± 3.6 2.9 3.6 28.0 ± 3.7 a: Includes claims for each antibiotic linked to the given diagnosis. In this analysis, if a single claim was eligible to be linked to multiple diagnoses, it was linked with only one diagnosis selected at random. b: Appropriateness of antibiotics for that diagnosis as determined by the CDC working group (see Methods) c: Adjusted value for 2011-2014 change from Poisson regression on claims per beneficiary per year adjusted for age, sex, race, census region, dual eligibility, and number of chronic conditions. Plus-minus contains 95% confidence interval. d: Includes Streptococcus pneumoniae pneumonia, other bacterial pneumonia, pneumonia due to other specified organism, pneumonia in infectious diseases classified elsewhere, bronchopneumonia with organism unspecified, pneumonia with organism unspecified e: Includes acute nasopharyngitis, acute laryngitis and tracheitis, acute upper respiratory infections of multiple or unspecified sites, and cough f: Includes bronchitis not specified as acute or chronic, acute bronchitis and bronchiolitis g: Includes chronic bronchitis, dyspnea, stridor, hemoptysis, and abnormal sputum h: Includes allergic rhinitis and unspecified allergy 10

Appendix Table 7. Trends in use of ciprofloxacin, metronidazole, and levofloxacin for gastrointestinal conditions. Claims per 1,000 beneficiaries per year a Ciprofloxacin Metronidazole Levofloxacin Antibiotics Diagnosis appropriate? b 2011 2014 change c 2011 2014 (%) change c 2011 2014 (%) change c (%) Infection d Potentially 36.4 32.9 6.5 ± 0.9 29.7 27.6 4.9 ± 0.9 16.8 19.5 20.3 ± 1.5 Other conditions e No 42.9 39.9 4.0 ± 0.8 29.3 28.6 0.8 ± 1.0 23.6 29.0 27.1 ± 1.3 a: Includes claims for each antibiotic linked to the given diagnosis. A single claim may be linked to multiple diagnoses, so the sum of the 2011 and 2014 columns exceeds the number of claims associated with any listed diagnosis (see main text Methods). b: Appropriateness of antibiotics for that diagnosis as determined by the CDC working group (see main text Methods) c: Adjusted value for 2011-2014 change from Poisson regression on claims per beneficiary per year adjusted for age, sex, race, census region, dual eligibility, and number of chronic conditions. Plus-minus contains 95% confidence interval. d: Includes intestinal infectious diseases, symptoms involving the abdomen or digestive system e: Includes other conditions of the digestive system 11

Appendix Table 8. Trends in use of ciprofloxacin, trimethoprim/sulfamethoxazole, and nitrofurantoin for genitourinary conditions. Claims per 1,000 beneficiaries per year a Ciprofloxacin TMP/SMX Nitrofurantoin Antibiotics Diagnosis appropriate? b 2011 2014 change c 2011 2014 (%) change c 2011 2014 (%) change c (%) Infection d Yes 92.9 83.2 6.4 ± 0.6 40.6 37.2 2.4 ± 0.8 44.8 38.3 7.0 ± 0.8 Other conditions e No 76.9 73.8 3.0 ± 0.6 30.1 30.6 4.8 ± 1.0 24.1 22.0 2.3 ± 1.1 a: Includes claims for each antibiotic linked to the given diagnosis. A single claim may be linked to multiple diagnoses, so the sum of the 2011 and 2014 columns exceeds the number of claims associated with any listed diagnosis (see main text Methods). b: Appropriateness of antibiotics for that diagnosis as determined by the CDC working group (see main text Methods) c: Adjusted value for 2011-2014 change from Poisson regression on claims per beneficiary per year adjusted for age, sex, race, census region, dual eligibility, and number of chronic conditions. Plus-minus contains 95% confidence interval. d: Includes acute pyelonephritis, renal abscess, other pyelonephritis/pyelonephrosis, unspecified kidney infection, acute cystitis, unspecified cystitis, and unspecified UTI e: Includes other symptoms involving urinary system, including dysuria 12

Appendix Table 9. Trends in use of cephalexin, trimethoprim/sulfamethoxazole, and ciprofloxacin for skin, cutaneous and mucosal conditions. Claims per 1,000 beneficiaries per year a Cephalexin TMP/SMX Ciprofloxacin Antibiotics Diagnosis appropriate? b 2011 2014 change c 2011 2014 (%) change c 2011 2014 (%) change c (%) Infection d Potentially 31.7 31.9 3.5 ± 1.0 22.5 22.1 2.1 ± 1.1 12.5 10.2 15.0 ± 1.3 Other conditions e No 44.2 46.6 7.4 ± 0.9 27.5 27.8 6.3 ± 1.1 34.5 31.9 3.9 ± 0.9 a: Includes claims for each antibiotic linked to the given diagnosis. A single claim may be linked to multiple diagnoses, so the sum of the 2011 and 2014 columns exceeds the number of claims associated with any listed diagnosis (see main text Methods). b: Appropriateness of antibiotics for that diagnosis as determined by the CDC working group (see main text Methods) c: Adjusted value for 2011-2014 change from Poisson regression on claims per beneficiary per year adjusted for age, sex, race, census region, dual eligibility, and number of chronic conditions. Plus-minus contains 95% confidence interval. d Includes cellulitis, carbuncle/furuncle, impetigo, lymphadenitis, erysipelas, dermatophytosis, folliculitis, myositis, mastitis, necrotizing fasciitis, and infective otitis externa e: Includes inflammatory and other skin conditions, open wounds, superficial injuries, burns, diseases of the eye/adnexa, ear diseases other than otitis media and mastoiditis, symptoms of skin/integumentary tissues excluding acne, gangrene, and enlargement of lymph node 13

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