Abstract
Background
Mecillinam, an amidinopenicillin antibiotic, has been used to treat urinary tract infections and bacterial enteritis in many countries. In this study, we evaluated in vitro activity of mecillinam against Enterobacteriaceae isolates from urine, and Salmonella and Shigella isolates from patients with bacterial gastroenteritis.
Materials and Methods
A total of 308 clinical strains were collected and were comprised of Escherichia coli (n=109), Klebsiella pneumoniae (n=52), Enterobacter spp. (n=30), Serratia marcescens (n=30) and Proteus spp. (n=29) isolated from a university hospital in Korea in 2007, and of Salmonella spp. (n=28) and Shigella spp. (n=30) isolated from Korean diarrheal patients from 2001 to 2006. Antimicrobial susceptibility was tested by Clinical Laboratory Standard Institute (CLSI) agar dilution method. CLSI breakpoint of mecillinam for E. coli urinary tract isolates was applied to all other isolates.
Results
In E. coli, rate of susceptibility to ampicillin was 30%, but 99-100% to amikacin and cefotaxime. Most (96%) of E. coli isolates, including extended-spectrum β-lactamase (ESBL) producers, were susceptible to mecillinam. All ESBL producers, except for one isolate, were inhibited by ≤4 µg/mL of mecillinam. MIC90 of mecillinam for K. pneumoniae and Enterobacter spp. was 8 µg/mL and 1 µg/mL, respectively, and the susceptibility rate was 92% and 97%, respectively. However, MIC90 of mecillinam for S. marcescens isolates was >128 µg/mL and most of them were resistant to mecillinam. All Salmonella isolates and 27 of 30 Shigella isolates were susceptible to mecillinam.
Figures and Tables
References
1. Farmer JJ 3rd. Murray PR, Baron EJ, Jorgensen JH, Pfaller MA, Yolken RH, editors. Enterobacteriaceae: Introduction and identification. Manual of clinical microbiology. 2003. 8th ed. Washington, D.C.: ASM press.
2. Koh EM, Lee SG, Kim CK, Kim M, Yong D, Lee K, Kim JM, Kim DS, Chong Y. Microorganisms isolated from blood cultures and their antimicrobial susceptibility patterns at a university hospital during 1994-2003. Korean J Lab Med. 2007. 27:265–275.


4. Lee JC, Jeong YS, Oh JY, Kang HY, Kim KH, Kim J, Lee YC, Cho DT, Seol SY. Epidemiology of shigellosis in Korea. J Bacteriol Virol. 2006. 36:41–49.


5. Lee YJ, Hwang UK, Kim JS, Kim JY, Koo JS, Lee BK, Kang JW. Epidemiologic investigation on sporadic occurrence of shigellosis in a subcounty of Cheongwon county in Chungbuk province in 2003. J Prev Med Public Health. 2005. 38:182–188.
6. Lee H, Kim CK, Lee J, Lee SH, Ahn JY, Hong SG, Park YJ, Jeong SH, Kim EC, Lee WK, Uh Y, Shin JH, Choi TY, Kwak HS, Lee K. Antimicrobial resistance of clinically important bacteria isolated from 12 hospitals in Korea in 2005 and 2006. Korean J Clin Microbiol. 2007. 10:59–69.
7. Lee H, Yong D, Lee K, Hong SG, Kim EC, Jeong SH, Park YJ, Choi TY, Uh Y, Shin JH, Lee WK, Lee J, Ahn JY, Lee SH, Woo GJ. Antimicrobial resistance of clinically important bacteria isolated from 12 hospitals in Korea in 2004. Korean J Clin Microbiol. 2005. 8:66–73.
8. Falagas ME, Grammatikos AP, Michalopoulos A. Potential of old-generation antibiotics to address current need for new antibiotics. Expert Rev Anti Infect Ther. 2008. 6:593–600.


9. Lund F, Tybring L. 6-amidinopenicillanic acids-a new group of antibiotics. Nat New Biol. 1972. 236:135–137.


10. Zhanel GG, Karlowsky JA, Schwartz B, Jensen SB, Hoban DJ. Mecillinam activity compared to ampicillin, trimethoprim/sulfamethoxazole, ciprofloxacin and nitrofurantoin against urinary tract isolates of gram-negative bacilli. Chemotherapy. 1998. 44:391–396.


11. Graninger W. Pivmecillinam-therapy of choice for lower urinary tract infection. Int J Antimicrob Agents. 2003. 22:Suppl 2. 73–78.


12. Skov R, Frimodt-Moller N, Menday P, Espersen F. Susceptibility testing of urinary isolates of Escherichia coli to mecillinam using NCCLS methodology. Int J Antimicrob Agents. 2005. 25:198–204.


13. Hossain MA, Rahman M, Ahmed QS, Malek MA, Sack RB, Albert MJ. Increasing frequency of mecillinam-resistant shigella isolates in urban Dhaka and rural Matlab, Bangladesh: A 6 year observation. J Antimicrob Chemother. 1998. 42:99–102.


14. CLSI. Performance standards for antimicrobial susceptibility testing; seventeenth informational supplement. M100-s17. 2007. Wayne, PA: Clinical and Laboratory Standards Institute.
15. Bryskier A. Antimicrobial agents: Antibacterials and antifungals. 2005. Washington: ASM Press.
16. Kang JH, Bae IK, Kwon SB, Jeong SH, Lee J, Lee WG, Kang JO, Ahn JY, Hong SG, Shin JH, Uh Y, Park YJ, Kim EC, Lee K, Yong D, Woo GJ. Prevalence of Ambler class A extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates in Korea. Korean J Clin Microbiol. 2005. 8:17–25.
17. Lee SG, Jeong SH, Lee H, Kim CK, Lee Y, Koh E, Chong Y, Lee K. Spread of CTX-M-type extended-spectrum β-lactamases among bloodstream isolates of Escherichia coli and Klebsiella pneumoniae from a Korean hospital. Diagn Microbiol Infect Dis. 2009. 63:76–80.


18. Hong SJ, Lee CH, Wang JH, Song W, Jung SH. Clinical characteristics of extended-spectrum β-lactamase producing Shigella sonnei infection out-breaked in Chungju area. Korean J Lab Med. 2006. 26:168–173.


19. Lee K, Yong D, Yum JH, Kim HH, Chong Y. Diversity of TEM-52 extended-spectrum β-lactamase-producing non-typhoidal Salmonella isolates in Korea. J Antimicrob Chemother. 2003. 52:493–496.


20. Lee K, Lee M, Shin JH, Lee MH, Kang SH, Park AJ, Yong D, Chong Y. Prevalence of plasmid-mediated AmpC β-lactamases in Escherichia coli and Klebsiella pneumoniae in Korea. Microb Drug Resist. 2006. 12:44–49.


21. Mazzulli T, Skulnick M, Small G, Marshall W, Hoban DJ, Zhanel GG, Finn S, Low DE. Susceptibility of community gram-negative urinary tract isolates to mecillinam and other oral agents. Can J Infect Dis. 2001. 12:289–292.


22. Kahlmeter G. An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: The ECO.SENS project. J Antimicrob Chemother. 2003. 51:69–76.


23. Sougakoff W, Jarlier V. Comparative potency of mecillinam and other β-lactam antibiotics against Escherichia coli strains producing different β-lactamases. J Antimicrob Chemother. 2000. 46:Suppl 1. 9–14. discussion 63-5.


24. Richmond MH. In vitro studies with mecillinam on Escherichia coli and Pseudomonas aeruginosa. J Antimicrob Chemother. 1977. 3:Suppl B. 29–39.


25. Nicolle LE, Mulvey MR. Successful treatment of CTX-M ESBL producing Escherichia coli relapsing pyelonephritis with long term pivmecillinam. Scand J Infect Dis. 2007. 39:748–749.


26. Brenwald NP, Andrews J, Fraise AP. Activity of mecillinam against AmpC β-lactamase-producing Escherichia coli. J Antimicrob Chemother. 2006. 58:223–224.


27. Thomas K, Weinbren MJ, Warner M, Woodford N, Livermore D. Activity of mecillinam against ESBL producers in vitro. J Antimicrob Chemother. 2006. 57:367–368.

