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1 w wz 15«2y Kor. J. Clin. Pharm., Vol. 15, No z s y e.pyjgmpybdjo $FQIBMPTQPSJO"[JUISPNZDJO Á w w w w Comparison of Monotherapy versus Cephalosporin - Combination Therapies for the Treatment of Community Acquired Pneumonia Eunjin Cheong and Sukhyang Lee Graduate School of Clinical Pharmacy, Sookmyung Women's University Chungpa-dong, Yongsan-gu, Seoul, , Korea Background and Objective Community acquired pneumonia (CAP) remains a prevalent and potentially life threatening illness. American Thoracic Society and Infectious Disease Society America recommend combination therapies with β- lactam plus a macrolide or a fluoroquinolone monotherapy for the empirical treatment of CAP. The aim of this study is to compare moxifloxacin monotherapy with cephalosporin plus azithromycin combination therapies. Methods From January 2004 to March 2005, 18 patients in the moxifloxacin group(mg) and 21 patients in the cefuroxime or ceftriaxone plus azithromycin group (CAG) with CAP were retrospectively reviewed with regard to clinical, laboratory and microbiological data. Each patient was stratified into mild (risk class I-II), moderate (risk class III) and severe (risk class VI, V) group according to PSI (Pneumonia Severity Index) score. Each group was compared for microbiological eradication, clinical assessment, the length of hospital stay, the period of s Results Total 39 patients with CAP were reviewed. The appropriateness of admission was 83.3% in MG vs. 76.2% in CAG. The mean length of the hospital day for 8.31 days vs days, days switching parenteral to oral antibiotics in 5.19 days vs days, clinical improvement in 2.43 days vs days in MG vs. CAG. Radiological improvement required 3.75 days vs 3.63 days in MG vs. CAG and bacteriological eradication rate at discharge was same in the both groups. Mortality rate was 11.1% (2 of 18) vs 14.3% (3 of 21) in MG vs. CAG (p=0.77). Drug cost of the mean 5 hospital days requiring parenteral antibiotics was the most inexpensive in moxifloxacin group for the 147,045 won, and ceftriaxone 1g-azithromycin group for the 170,285 won, cefuroxime bid-azithromycin gruop for the 207,800 won, ceftriaxone 2g-azithromycin group for the 220,570 won, cefuroxime tid-azithromycin group for the 251,700 won. There was no significant statistical difference in clinical, bacterial, radiological cure and hospital days, and switch to oral days. Conclusion It was concluded that i.v. moxifloxacin monotherapy was as effective as azithromycin plus cefuroxime or ceftriaxone combination therapies for the treatment of CAP. In drug cost analysis, moxifloxacin is less expensive than CAG. Key words Community Acquired Pneumonia,,, Ceftriaxone, Cefuroxime z s w» e wš w ³ ü ³ x e Correspondence to : w w w w Tel: , Fax: slee@sdic.sookmyung.ac.kr š. 1 4 wš 1/4 w. e e ƒw» w» y w ƒ z w y ù ƒ w. 1,2) Infectious Disease Society 2000 tw guideline z s w e e wš. ³ x 3) 1

2 2 Kor. J. Clin. Pharm., Vol. 15, No. 2, 2005» 8 e w x w β-lactam w macrolide w ù fluoroquinolone e wš. 4 quinolone w moxifloxacin cephalosporin 2 cefuroxime y 3 ceftriaxone macrolide w azithromycin e z sƒwš w. y l ¾ 3» n pneumonia 18 y 202 {» s s y ƒ moxifloxacin IV n azithromycin cephalosporin cefuroxime ceftriaxone y w. s 48 w y q y w. moxifloxacin IV (Avelox 400 mg, Bayer Korea)n 18 cefuroxime (Alporin 750 mg, GlaxoSmithKline) azithromycin IV (Zithromax 500 mg, Pfizer) n 16, ceftriaxone (Ceftriaxone 1 g, DaeHwa) azithromycin IV (Zithromax 500 mg, Pfizer) n 5 21 zw w. w n 400 mg 1 1z IV n š azithromycin 500 mg 1 1z IV n. Cefuroxime 1500 mg 1 2z 3z IV n š ceftriaxone 1g 2g 1 1z IV n. e z» w y»» w»e y, y š, m»», x ƒ w», s y» w ³w e z w. y»e n ¾ ƒ y š, m y w.» w x w.» p w» n, lactuloseù magnesium oxide, y y ù y» itopride, domperidone, metoclopramide d w. pheniramine, l š q w. e w AST, ALT» Scr, BUN» sƒ w.» e ù z w ù,» y» w w. sƒw y p, s, ³,, ³w, z,», w y»,, n, w x z s y e xy š z w š w. m m SAS V8 v w pooled t-test w p 0.05 w m w q w. y p (18 ) û ƒ 66.7% (12/18) š cephalosporin azithromycin (21 ) û ƒ 61.9% (13/21) š, s³ ƒƒ 67.9 (range 43-85) 63.6 (range 24-84). ƒ 2/3 x (66.7%, 66.7%).(Table 1) y COPD ƒ š w ù, š x,,,, s»,» y y w w. y»»e, š y š y w. y {m ƒ w ù w Table 1. s y p (n=18) No(%) Cephalosporin + (n=21) No(%) Sex, male 12 (66.7%) 13 (61.9%) 0.76 Mean age, year(range) 67.9 (43-85) 63.6 (24-84) 0.35 smoking history 12 (66.7%) 14 (66.7%) 1 Past or present alcohol 7 (38.9%) 9 (42.9%) 0.55 Diabetes 2 (11.1%) 4 (19%) 0.50 Hypertention 6 (33.3%) 6 (28.6%) 0.75 Old TB* 8 (44.4%) 6 (28.6%) 0.31 COPD** 9 (50%) 7 (33.3%) 0.30 Asthma 3 (16.7%) 3 (14.3%) 0.84 Emphysema 4 (22.2%) 3 (14.3%) 0.53 Bronchiectasis 3 (16.7%) 2 (9.5%) 0.51 Chronic renal failure 3 (16.7%) 2 (9.5%) 0.51 *Old TB - Past tuberculosis history **COPD - Chronic obstructive pulmonary disease

3 z s y e Cephalosporin - 3 Table 2.» n=18, Cephalosporin + n=21, No(%) No(%) Cough 17 (94.4%) 19 (90.5%) 0.65 Dyspnea 14 (77.8%) 15 (71.4%) 0.66 Sputum 15 (83.3%) 15 (71.4%) 0.39 Chest pain or 4 (22.2%) 7 (33.3%) 0.45 discomport Fever or chill 16 (88.9%) 19 (90.5%) 0.87 Right flank pain 3 (16.7%) 2 (9.5%) 0.51 m y w» w (Table 2). y» p y,» w. s s (Pneumonia Severity Index, PSI) sƒ moxifloxacin n e ƒ ƒ w x (I, II) 3, e ƒ ƒ w III 6, š x (IV, V) %ƒ w cephalosporin azithromycin x (I,II) 5, III 5, š x (IV, V) %ƒ w š sƒ.(table 3) s ³ ³ ƒ x moxifloxacin(mg) n 18 9 (50%) š cephalosporin-azithromycin(cag) (47.6%). s ³ moxifloxacin n S. pneumoniaeƒ 2, K. pneumonia 2, P. aeroginosaƒ 1, Acinetobacterƒ 2, Candida albicansƒ 1, S. aureus 1, 9 š cephalosporin azithromycin S. pneumoniaeƒ 3, K. pneumonia 2, P. aeruginosaƒ 1, Acinetobacterƒ 1, Candida albicansƒ 2, S. aureusƒ 1, escheria coliƒ 1, enterobacter cloaceae³ 1, 11. n S. pneumonia K. pneumonia, acinetobacter³ ƒ š, cephalosporin Table 3. sƒ (PSI- Pneumonia Severity Index ) n=18, No(%) Cephalosporin + n=21, No(%) I 1 (6%) 2 (10%) 0.65 II 2 (11%) 3 (14%) 0.84 III 6 (33%) 5 (24%) 0.78 IV 6 (33%) 9 (43%) 0.55 V 3 (17%) 2 (10%) 0.51 azithromycin S. pneumoniae K. pneumonia, Candida albicans ³.(Table 4) Mycoplasma pneumonia y 2 ù w negative ù. ³ z ³ ƒ y z w yw moxifloxacin 3 ƒ š 2 ƒ. ³w e z w»e, y š, m» moxifloxacin 2.43, 2.61 š w (p= 0.71).(Table 5) š y» moxifloxacin 2.86, 3.0 š w (p=0.84). WBCƒ» moxifloxacin 4.89, 3.21 š w (p=0.26). ƒ y» w» moxifloxacin 3.75, 3.63 š w (p=0.89). ³w e ³ ƒ x moxifloxacinn 10 w 2 n ³ 1 ³ 2 wš n ³ w Table 4. s ³ Microbiology n=18, No Cephalosporin + n=21, No Streptococus pneumoniae 2 3 Klebsiella pneumonia 2 2 Pseudomonas aeruginosa 1 1 Acinetobacter 2 1 Candida albicans 1 2 Staphylcoccus aureus 1 1 Enterobacter cloacae 0 1 Escherichia coli 0 1 Not identified 9 11 Table 5.», y»,» n=18, days* Cephalosporin + n=21, days* Length of hospital 8.31± ± Switch to oral 5.19± ± Clinical improvement 2.43± ± Fever down 2.86±2.1 3± WBC normalization 4.88± ± Radiological improvement 3.75± ± Mortality, No (%) 2 (11.1%) 3 (14.3%) 0.77 *Days were presented as the mean Û SD

4 4 Kor. J. Clin. Pharm., Vol. 15, No. 2, 2005 y š (70% cure), ³ ƒ x 10 w 3 n ³ 2 wš ³ w y (70% cure). ³ e ƒ k n w moxifloxacin 1 n 3 z w, ³ S. pneumoniae. y 2 (11.1%) š y 3 (14.3%) sepsis w w (p=0.77).» w y» s³» y 2 w š 8.31 š y 3 wš 7.39 w (p=0.56).(table 5) w y» moxifloxacin 5.19, 5.28 š w (p =0.91). moxifloxacin 50% (9 of 18) š 43% (9 of 21) ù m (p=0.66). 12 wš 18 w ƒƒ (11%, 0%, p<0.01), y (17%, 19%, p=0.84), (0%, 9.5%, p<0.01), AST (aspartate transaminase), ALT (alanine transaminase) z (17%, 24%, p=0.59), Scr (serum creatinine), BUN (blood urea nitrogen) (5.6%, 14.3%, p=0.08), alkaline phosphatase (16.7%, 14.3%, p=0.76), (0%, 5%, p<0.01). (Table 6) w w w ¼ 2 w yw. ASTù ALT z eƒ w flavine adenine dinucleotide adelavin ù silymarin y w ù w y w. ³ z yw w z z eƒ 1. Scr ù BUN w moxifloxacin 1, 3 2 ƒ» y» l eƒ k š» y moxifloxacin 1 1 ƒ sepsis azotemia w. n y 2 27 w 1 w 15 n w. Macrolide ƒ (7 ), fluoroquinolone (6 ), macrolide + fluoroquinolone (2 ) š Table 6.» 7 ƒ (range, 5-20).(Table 7) y 3 w n y 18 w macrolide w ƒ (13 ) 3 cephalosporin + macrolide (2 ), 2 cephalosporin + macrolide (1 ), 2 cephalosporin (1 ), β-lactam/β-lactamase inhibitor (1 ) š» 7 (4-8 ) ƒ.»e ƒ n w ¾ û moxifloxacin n y (69%), (78%)»e Codenal Cough Mucopect ù Letozo. sƒ (Avelox, Bayer Korea) 400 mg 1 vial ƒ š ƒ 29,409 š, azithromycin (Zithromax, Pfizer) 500 mg 1 vial ƒ 24,000 š, cefuroxime (Alporin, GlaxoSmithKline) 750mg 1 vial ƒ 4,390, ceftriaxone (Ceftriaxone, DaeHwa) 1 g 1 vial ƒ 10, ,409 š cefuroxime azithromycin cefuroxime 1 2z n 41,560 š 3z n 50,340. Ceftriaxone azithromycin ceftriaxone 1z 1g n 34,057 š 2g n 44,114. n=18, No(%) Cephalosporin+ n=21, No(%) 2 (11%) 0 <0.01 y 3 (17%) 4 (19%) (9.5%) <0.01 AST, ALT 3 (17%) 5 (24%) 0.59 Scr, BUN 1 (5.6%) 3 (14.3%) 0.08 Alkaline phosphatase 3 (16.7%) 3 (14.3%) (5%) <01 9 (50%) 9 (43%) 0.66 Table 7. n w xy Antibiotics n=18, No Cephalosporin + n=21, No Macrolide 7 13 Fluoroquinolone 6 0 Macrolide + Fluoroquinolone 2 0 Cephalosporin 2 rd generation 0 1 Cephalosporin 2 rd + Macrolide 0 1 Cephalosporin 3 rd + Macrolide 0 2 β-lactam/ β-lactamase inhibitor 0 1 Missing 1 0

5 z s y e Cephalosporin - 5 s³ n ƒ 5 5 n moxifloxacin 147,045 ƒ w š ceftriaxone 1g azithromycin 170,285, cefuroxime 2 z n azithromycin 207,800, ceftriaxone 2g azithromycin 220,570, cefuroxime 3z n azithromycin 251,700 ùkû. š y p r moxifloxacin cephalosporin, azithromycin û š (66.7%, 61.9%) s³ ƒƒ y š û y x w š x sw. w p (66.7%). s y w ù»e,, y š, {m w ƒ. s y s š ù w» ƒ w ƒ š tw w. 4 y 5 w û 3, 2 (moxifloxacin û ƒ 1, cephalosporin azithromycin û 2, 1 ) š œm y š, š. IDSA y,, š,, x s y ƒ 3) š w w. w s³ ù 77 (moxifloxacin s³ 72, cephalosporin azithromycin s³ 80.3 ) š š s³ 28 (moxifloxacin 25, cephalosporin azithromycin 30 )» ú f. m w (p<0.01» (p<0.01) w. ù ƒ,» ú x f. wz 2000 tw s e e w. 50 w y (,, x y, y, y) š yƒ, 125, y 30,» x 90 mmhg w, 35 o C w ù 40 o C Class I wš 50 w w w w Class II l V¾ w Class I, II e, III» e, IV, V e w «wš. 3) w moxifloxacin 83.3%, cephalosporin azithromycin 76.2%ƒ ww. y 5 1 IV, 4 V w ƒ f e w. 3) s ³ moxifloxacin 9 50% š azithromycin % 1999 PORT 29.6%. 4) ³ s x, bronchial washing ƒ 1 wš sputum š ³, ³, q ³ w s S. pneumoniae, K. pneumonia ƒ. S. pneumoniaeƒ s ³ w. š e ƒ ¼ Mycoplasma pneumoniaù Legionella³ x³ w. P. aeruginosa, S. aureus, Acinetobacter, Escherichia coli ³ ƒ. y 5» ú w ³ x, catheter urine š p ü ³ p. (, imipenem, meropenem, ceftazidime w Pseudomonas aeruginosa Stenotrophonas maltophilia, open pus ciprofloxacin, ceftazidime w š cefotaxime, imipenem Proteus mirabilis ) ³ ƒ y z w yw moxifloxacin 2 ƒ, 1 ³ Acinetobacter iwofii 7 z cefuroxime azithromycin yw š y z z. 1 w. Cephalosporin azithromycin 2 ƒ ü x š. z 3 ü y š,,»e, {m š ƒ y. WBCƒ» ƒ y» 3~4 ü y. k ¾ x 3, x 4, š x 6 s ³ 3~4 w ù. 5) w y» s³ 5 š w yw n w. moxifloxacin 50% (9/18) š azithromycin 43% (9/21) ù m (p=0.66). moxifloxacin 12, azithromycin 18 w m ù cephalosporin azithromycin ƒw ù. y alkaline phosphatase e y» y w. n s e w cephalosporin 3 2, macrolide, fluoroquinolone ƒ. 6) n macrolide ƒ š fluoroquinolone, macrolide fluoroquinolone, cephalosporin 3

6 6 Kor. J. Clin. Pharm., Vol. 15, No. 2, 2005 macrolide, cephalosporin 2 macrolide, cephalosporin 2, β-lactam/ β-lactamase inhibitor e w š» 7 ƒ.»e ƒ n w ¾ û moxifloxacin 69%, cephalpsporin azithromycin 78%ƒ»e Codenal ¾ Cough Mucopect ù Letozol. s³ n 5 moxifloxacin 147,050 ƒ wš ceftriaxone 1 g azithromycin 170,285, cefuroxime 2z n azithromycin 207,800, ceftriaxone 2g azithromycin 220,570, cefuroxime 3z n azithromycin 251,700 ùk û. w š w š»ù line e w n z ƒ moxifloxaxin w. quinolone ü ƒƒ š š š (yg,, ) CDC (Centers for Disease Control and Prevention) s 1 quinolone ww «wš s ³ w ü p kw w. 3,7) 400mg qd IV (Avelox, Bayer Korea)n cephalosprin ceftriaxone (Ceftriaxone, DaeHwa) 1 ~2 g qd cefuroxime (Alporin, GlaxoSmithKline) 1500 mg bid/tid azithromycin 500mg IV (Zithromax, Pfizer) r, ³w, z, w y» ƒ ùkù z w. moxi-floxacin 50% (9 of 18) š azithromycin 43% (9 of 21) ù m. sƒ cephalosporin azithromycin w w e ùkü. š x 1. Niederman MS, McCombs JS, Unger AN, et al. The cost of treating community acquired pneumina. Clin Ther 1998; 20: Halm EA, TeiRstein AS. Management of communityacquired pneumonia. N Engl J Med 2002; 347: Bartlett JG, Dowell SF, Mandell LA, et al. Practice Guidelines for the management of community-acquired pneumonia in adults. Clin Infect Dis 2000; 31: Fine MJ, Stone RA, Singer DE, et al. Processes and outcomes of care with community-acquired pneumonia. results from the pneumonia patient outcomes research team (PORT) cohort study. Arch Intern Med 1999; 10: 159: Halm EA, Fine MJ, Marrie TJ, et al. Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines. JAMA 1998; 279: Niederman MS, Mandell LA, Anzueto A, et al. American Thoracic Society.: Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med 2001; 163: , ½,,. z z s ( s ) e w w e. Chung- Ang J Med 2003; 28: Avelox, DC ( z), Bayer Korea 9. Fine MJ, Auble TE, Yearly DM, et al. A prediction rule to identify low-risk patients with community acquired pneumonia. N Engl J Med 1997; 336: Katz E, Larsen LS, Fogarty CM, et al. Safety and efficacy of sequential i.v. to p.o. moxifloxacin versus conventional combination therapies for the treatment of community-acquired pneumonia in patients requiring initial i.v. therapy. J Emerg Med. 2004; 27: Zithromax, DC ( z), Pfizer 12. Alporin, DC, GlaxoSmithKline 13. Ceftriaxone, DC, DaeHwa 14. Bartlett JG, Mundy LM. Current concepts: Communityacquired pneumonia. N Engl J Med 1995;333: Kinasewitz G, Wood RG. versus cefaclor in the treatment of acute bacterial pneumonia. Eur J Clin Microbiol Infect Dis 1991; 10: Fine MJ, Smith DN, Singer DE. Hospitalization decision in patients with community-acquired pneumonia: a prospective cohort study. Am J Med 1990; 89: BTS Guidelines for the Management of Community Acquired Pneumonia in Adults. Thorax 2001; 56 (Suppl 4): Mandell LA, Marrie TJ, Grossman RF, et al. The Canadian CAP Working Group. Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society. Clin Infect Dis 2000; 31: Metlay JP, Schulz R, Li YH, et al. Influence of age on symptoms at presentation in patients with community-

7 z s y e Cephalosporin - 7 acquired pneumonia. Arch Intern Med 1997; 157: Farr BM, Kaiser DL, Harrison BDW, et al. Prediction of microbial aetiology at admission to hospital for pneumonia from the presenting clinical features. Thorax 1989; 44: Halm EA, Fine MJ, Kapoor WN, et al. Instability on hospital discharge and the risk of adverse outcomes in patients with pneumonia. Arch Intern Med 2002; 162; x. z s Cefodizime z Ceftriaxone w. 1994; 26: x, Pneumonia Severity Index z s y e xy. w w w w , z z s e. Inje Medical Journal 2002; 23;

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16(1)-3(국문)(p.40-45).fm w wz 16«1y Kor. J. Clin. Pharm., Vol. 16, No. 1. 2006 x w$btf3fqpsu'psn û w m w Department of Statistics, Chonnam National University Eunsik Park College of Natural Sciences, Chonnam National University