長久以來，因為國人不當濫用抗生素，已使我國成為抗藥性嚴重地區，由於抗生素的過度使用，使得抗藥性菌株充斥於環境中。此外，畜產及養殖業的發達，密集養殖之結果，疾病叢生，許多業者在飼料中大量加入抗生素以預防或治療疾病，而其排廢水並無適當的處理，隨著排水溝流入河川或土壤之中，而造成抗藥性菌株形成與散佈。抗藥性細菌藉此廣泛存於環境中，並藉由細菌間之接合作用擴散抗藥性，嚴重威脅人類的生命且造成醫療保健上的困擾。除醫療用的抗生素外，工業污染與農業污染對環境及生態造成的影響甚鉅，其中對人類健康最有影響的是重金屬類、氰化物及人類合成的有機毒物如農藥、多氯聯苯、戴奧新等。
本實驗採集了台灣南部地區之工業區、廢五金工廠、魚池、菜園、果園及河川之土壤、水中之綠膿桿菌。分析各綠膿桿菌株對各種抗生素及各農藥之抗藥性及對重金屬汞（Hg）、鎘（Cd）、砷（As）、鉻(Cr)等離子之耐受性。期能藉由分析之結果，瞭解抗生素濫用及產業對環境污染之嚴重性。分析結果顯示分離環境綠膿桿菌菌株對抗生素中Cefoperazone抗性比例約達40 %，Tobramycin的抗性比例約為20 %，而Imipenem、Ceftazidime的抗性比例均約為4 %最低。於重金屬鹽類中，以Hg的抗性比例最高達約27 %，AS次之其抗性比例約為10 %，Cr呈感受性其抗性比例為0 %。農藥試驗中以巴拉刈(Paraquat)抗性比例最高，達約36 ﹪，培丹(Cartap)、納乃得(Methomyl)呈感受性其抗性比例為0 %。
綜合本實驗之結果，目前環境中綠膿桿菌的抗性菌株並不普遍，如何防止環境中抗性菌株之擴散，有賴於醫師及藥師對抗生素之審慎使用及國人在服藥上的服從性之加強。而在農畜產方面，農藥、抗生素等之節制使用，及在產業界加強環境污染管制，即能控制環境中抗性菌株之擴散。

In the present work, in order to evaluate the seriousness of environmental pollution caused by antibiotics abuse, and by industrial and agricultural pollutants, different strains of Pseudomonas aeruginosa were collected from industrial area, abandoned metal hardware factory, fishery pool, vegetable garden and fruit farm, river mud, and different origins of water bodies in southern Taiwan. The organisms were analyzed for their drug resistance against a variety of antibiotics and agricultural pesticides. They were also analyzed for endurance toward heavy metal ions including mercury, cadmium, arsenic and chromium ions.

As the data indicated that, in terms of their resistance to clinical frequently used antibiotics, about 40% of the Pseudomonas aeruginosa isolates of the environment have developed resistance against Cefoperazone, about 20% showed resistance against Tobramycin, and only about 4% revealed resistance against Imipenem and Ceftazidime. As to heavy metal ion resistance, about 27% of the environmental Pseudomonas aeruginosa strains demonstrated resistance against mercury ion, and about 10% exhibited resistance against arsenic ions, whereas no resistance was observed toward chromium ions. In terms of resistance to agricultural pesticides, about 36% environmental isolates demonstrated resistance against Paraquat, but none of the tested Pseudomonas aeruginosa show resistance toward Cartap and Methomyl.

To sum up the findings, so far only minor portion of Pseudomonas aeruginosa acquired drug resistance, therefore, immediate measure is required to prevent the spreading of drug-resistant Pseudomonas aeruginosa . It is suggested that all the physicians and pharmacists to prescribe antibiotics should be more careful and responsible manner. Meanwhile, it would also call on the restrained usage of pesticides and antibiotics in the livestock and aquatic product industry, and strengthening pollution control in the industrial sector.

摘要…………………………………………………………………………2

緒言…………………………………………………………………………4

材料與方法…………………………………………………………………9

結果…………………………………………………………………………15

討論…………………………………………………………………………19

附圖…………………………………………………………………………23

附表………………………………………………………………………….27

附錄…………………………………………………………………………36

參考文獻……………………………………………………………………38

[1] M. Harada et al.: Methylmercury level in umbilical cords from patients with congenital Minamata disease. The Science of the total environment. 1999；234:59-62.
[2]黃錦章：有機汞中毒，台灣醫學，1997；1:1:119-123.
[3] Tien-chun Chang, : Higher Prevalence of Goiter in Endemic Area of Blackfoot Disease of Taiwan., Journal of the Formosan Medical Association. 1911；90 :10:941-946.
[4]阮國棟：砷之污染特性及處理技術：工業污染防治，1986；5:2:156-165.
[5] R. Lauwerys: The Chemistry, Biochemistry and Biology of Cadmium. In: M. Webb (editors) Cadmium in man., Elsevier/North Holland Biomedical Press, New York, NY. 1979；444-447.
[6] K. Nogawa, : Itai-Itai disease and fllow-up studies. In: J.O. Nriagu (editors): Cadmium in the Environment, John Wiley and Sons, New York, NY. 1981；1-37.
[7] X.W. Luo, S.C. Foo, and H.Y. Ong: Serum DDT and DDE levels in Singapore general population. The Science of the Total Environment 208. 1997；97-104.
[8] G..Z. Hang, Y.S. Min, B.X. Mai, G.Y. Sheng, J.M. Fu and Z.S. Wang : Time Trend of BHCs and DDTs in a Sedimentary Core in Macao Estuary, Southern China. Marine Pollution Bulletin. 1999；39 : 326-330.
[9]台灣區農藥工業同業公會會訊. 台灣區農藥工業同業公會. 1987；48.
[10] R.E. Green, Pesticide-Clay-Water interactions, In. W.D. Guenzi, (editor.): Pesticides in soil and Water. Soil Science Society of America, Inc. Madison, Wiscconsin. 1974；3-33.
[11] W.A. Jury et al.: Transport and transformations of organic chemicals in the soil-air- water ecosystem. In: G.W. Ware (editors), Reviews of environmental contamination and toxicology., Springer-Verlag New York. Inc. 1987；99 :121-146.
[12] D.L. Kinska, and P.H. Guilligan: Pseudomonas. In: P. Murray (editor). Manual of clinical microbiology.Washington, DC: ASM Press, 1999；517-525.
[13] J. T. Cheng：Pharmacology for clinical Practice. FARSEEING Book Co. Taipei,
Taiwan. 1991；1044-1045.
[14] M.G. Cormica and R.N. Jones: Emerging resistance to antimicrobial agents in Gram-positive bacteria: enterococci, staphylococci, and nonpneumococcal streptococci. Drugs. 1996；51(suppl 1) : 6-12.
[15] G.V. Doem, A. Brueggemann, H.P.Jr. Holley, and A.M. Rauch: Antimicrobial
resistance of Pseudomonas aeruginosa recovered from outpatients in the United States during the winter months of 1994 to1995：results of a 30-center national surveillance study. Antimicrob Agents Chemother. 1996；40 :1208-1213.
[16] M.A.E. Herbert, and R.E. Moxo:.Haemophilus influenzae.In: V.L.Yu, T.C. Merrigan, and S.L. Barriere (editors): Antimicrobial Therapy and Vaccines.Baltimore, Williams and Williams Wilkins.1999；213-227.
[17] R.N.Jones, E.N. Kehrberg, M.E. Erwin, S.C. Anderson: The Fluoroquinolone
Resistance Surveillance Group.Prevalence of important pathogens and antimicrobial activity of parenteral drugs at numerous medical centers on the United States I. Study on the threat of emerging resistances:real or perceived？ Diagn Microbiol Infect Dis.1994；19 :203-215.
[18] J.Z. Jordens, and M.P. E. Slack: Haemopilus influenzae: then and now. Eur. J. Clin. Microbiol. Infect. Dis. 1995；14 : 935-948.
[19] K.P. Klugman: Epidemiology, control, and treament of multiresistant pneumococci Drugs. 1996；52 (suppl 2):42-46.
[20] A.L. Panlilio, D.H. Culver, R.P. Gaynes, S. Banerjee, T.S Henderson, J.S. Tolson, and W.J. Marton: The National Nosocomial Infection Surveillance System. Methicillin-resistant Staphylococcus aureus in US hospitals, 1975-1991. Infect Control Hosp. Epidemiol. 1992；13 :582-586.
[21] A. Voss, and B.N. Doebbeling: The worldwide prevalence of methicillin-resistant Staphylococcus aureus. Int. J. Antimicrob. Agent. 1995；5 :101-106.
[22] A. Voss, D. Milatovic, C. Wallrauch-Schwarz, V.T. Rosdahl, and L. Braveny:
Methicillin-resistance Staphylococcus aureus in Europe. Eur. J. Clin. Microbiol. Infect Dis. 1994；13:50-55.
[23] S.C. Chang et al.: High prevalence of antibiotic resistance of common pathogenic bacteria in Taiwan. Diagnostic Microbiology and Infectious Disease. 2000；36 :107-112.
[24] A.C. Gales, R.N. Jones, J. Turnidge, R. Rennie, and R. Ramphal: Characterization of Pseudomonas aeruginosa Isolates：Occurrence Rates,Antimicrobial Susceptibility Patterns, and Molecular Typing in the Global SENTRY. Antimicrobial Surveillance Program, 1997-1999. Clinical Infectious Disease. 2001；32(Suppl 2):S146-55.
[25] A. Harris, C. Torres-Viera, L. Venkataraman, P. DeGirolami, M. Samore, Y.Carmeli: Epidemiology and clinical outcomes of patients with multi-resistant Pseudomonas Aeruginosa. Clin Infect Dis. 1999；28 :1128-1133.
[26]E. Jawetz, J. L. Melnick, E. A. Adelberg : Review of Medical Microbiology. Lange Medical Publications, California, USA. 1984；16:243-248.
[27] S. Iida, J. Meyer, and W. Arber: Prokaryotic IS elements, In: J.A Shapiro (editor), Mobile genetic elements., Academic Press, Inc., New York., 1983；159-221.
[28] N. Masuda, E. Sakagawa, and S.Ohya: Outer membrane proteins responsible for multiple drug resistance in Pseudomonas aeruginosa., Antimicrob Agents Chemother. 1995；39 :645-649.
[29] J.R. Aires, T. Kohler, H. Nikaido, P. Plesiat: Involvement of an active efflux system in the natural resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob Agents Chemother. 1999；43 :2624-2628.
[30] S. Jalal, and B. Wretlind: Mechanisms of quinolone resistance in clinical strains
of Pseudomonas aeruginosa. Microb. Drug Resist. 1998；4 :257-261.
[31] R. Srikumar, T. Kon, N. Gotoh, K. Poole: Expression of Pseudomonas aeruginosa multidrug efflux pumps MexA-MexB-OprM and MexC-MexD-OprJ in multidrug- sensitive Escherichia coli strain. Antimicrob. Agents Chemother. 1998；42:65-71.
[32] T. Takenouchi, E. Sakagawa, M. Sugawara: Detection of gyrA mutations among 335 Pseudomonas aeruginosa strains isolated in Japan and their susceptibilities to fluoro- quinolones. Antimicrob. Agents Chemother. 1999；43:406-409.
[33] A.S. Levin, A.A. Barone, and J. Penco: Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clin. Infect Dis. 1999；28:1008-1011.
[34] N. Gotoh, K. Tsujimoto, J. Poole, I. Yamagishi, and T. Nishino: The outer membrane protein OprM of Pseudomonas aeruginosa is enecoded by OprM of the mexA mexB OprM multidrug resistance operon. Antimicrob. Agents Chemother. 1995；39:2567-2569.
[35] K. Poole, K. Kredes, C. McNally, and S. Neshat:.Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an effluxoperon. J. Bacteriol. 1993；175:7363-7372.
[36] Z. Tynecka, Z. Gos, and J. Zajac: Reduced cadimium transport determined by a
resistant plasmid in Staphylococcus aureus. J. Bacteriol. 1981；147:305-312.
[37] E. Solh, J.M. Fouace, Z. Shalita, D.H. Bouanchaud, R.P. Novick, and Y.A. Chabbert. Epidemiological and structural tobramycin and streptomycin. Plasmid. 1980；4:117-120.
[38] A.A. Weiss, S.D. Murphy, and S. Silver:.Mercury and organomercuri al resistances determined by plasmids in Staphylococcus aurrus. J. Bacteriol. 1977；132:197-208.
[39] B.H. Belliveau, J.T. Mercury.,：Resistance and detoxification in bacteria., Appl.
Organometal. Chem. 1989；3:283-294.
[40] Silver, Simon.,：Bacterial resistances to toxic metal ions. Gene., 1996；1:9-19.
[41] C. Carlos et al.,：Interactions of chromium with microorganisms and plants.,
FEMS Microbiology Reviews. 2001；25:335-347.
[42]C. P. Chen：Experiment of Microbiology. Rey-Yu Book Co. Ping-Tung, Taiwan.
1985；190-199.
[43]M. Z. Zheng：Experimental Procedures for Medical Microbiology. Yi-hsien
Book Co. Taipei, Taiwan. 1998；256-257.
[44]C. P. Chen et al.,：Exoenzymes production antibiotic and heavy metal resistance
of Pseudomonas aeruginosa isolated from environments. Tajen Ann. Bull.
1995；13:01-14.
[45] J.S. Kahan, F.N.Kahan, E.O. Stapley, R.T. Goegelmen and S. Hernander.,
US patent, 3950357. 1976.
[46] J. T. Cheng：Pharmacology for clinical Practice. FARSEEING Book Co. Taipei,
Taiwan. 1991；979-984.
[47]環保署.二仁溪流域現存重金屬污染移除工作調查及規劃實施計劃第二次
期中報告.1992；2:54-83.
[48]環保署.台南縣水污染防治實施方案規劃（二仁溪）期末報告.1994；6:1-34.
[49]G. Viniegra et al.,：Chronic Arsenic Poisoning in the Lake Region. Section 4,
Treatment of Drinking Water. Water Poll. Abstr. 1965；38 : 430-431.
[50]Y. S. Shen et al.,：Relation between black-foot disease and the pollution of
drinking water by arsenic in Taiwan. Proc. 2nd Internat Conf. Wat. Poll.
Research. 1964；1:173-190.
[51]C. P. Chen：Modern Toxicology. Ho-Chi Book Co. Taipei, Taiwan. 2000；269.
[52]S. Silver and M. Walderhaug.,：Gene regulation of plasmid and chromosome-
determined inorganic ion transport in bacteria. Microbiol. Rev. 1992；56:
195-228.
[53] Z. R. Liu：Basic Toxicology. Yi-hsien Book Co. Taipei, Taiwan. 2001；323.