|Year : 2016 | Volume
| Issue : 6 | Page : 229-233
Antimicrobial activities of cefoperazone-sulbactam in comparison to cefoperazone against clinical organisms from medical centers in Taiwan
Tsung-Ta Chiang1, Hung-Jen Tang2, Cheng-Hsun Chiu3, Te-Li Chen4, Mao-Wang Ho5, Chen-Hsiang Lee6, Wang-Huei Sheng7, Ya-Sung Yang1
1 Department of Internal Medicine, National Defense Medical Center, Division of Infectious Diseases and Tropical Medicine, Taipei, Taiwan, China
2 Department of Medicine, Chi Mei Medical Center; Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, China
3 Department of Pediatrics, Chang Gung Children's Hospital and Chang Gung University, Taoyuan, Taiwan, China
4 National Defense Medical Center, The Graduate Institute of Life Sciences, Taipei, Taiwan, China
5 Department of Internal Medicine, Division of Infectious Diseases, China Medical University Hospital, Taichung, Taiwan, China
6 Department of Internal Medicine, Kaohsiung Medical Center, Division of Infectious Diseases, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, China
7 Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan, China
|Date of Submission||03-Jul-2016|
|Date of Decision||19-Sep-2016|
|Date of Acceptance||18-Oct-2016|
|Date of Web Publication||21-Dec-2016|
Department of Internal Medicine, National Defense Medical Center, Division of Infectious Diseases and Tropical Medicine, Tri-Service General Hospital, No. 325, Section 2, Cheng-Kung Road, Taipei 11490, Taiwan
Source of Support: None, Conflict of Interest: None
Background: The multidrug-resistant Gram-negative bacteria (MDRGNBs) have emerged as important pathogens recently. Cefoperazone-sulbactam is active against a great proportion of those MDRGNBs. However, the susceptibilities data of cefoperazone-sulbactam are lacking in Taiwan. Object: This study was conducted to evaluate the susceptibilities data of cefoperazone-sulbactam aganist commonly encountered clinical pathogens in Taiwan. Materials and Methods: 2272 isolates were collected from various clinical specimens from five centers in Taiwan in 2012. The agar dilution method was used to evaluate the susceptibility of the isolated pathogens to cefoperazone and cefoperazone-sulbactam. Result: cefoperazone-sulbactam showed better activity against various GNBs, including MDRGNBs and part of carbapenem-resistant isolates tested compared to cefoperazone alone. Conclusion: Cefoperazone-sulbactam is active against most commonly encountered clinical pathogens, including MDRGNBs and part of carbapenem-esistant A. baumannii complex. It can be a potentially therapeutic agent for treating infections caused by these pathogens in Taiwan.
Keywords: Antibiotic, cefoperazone, resistance, susceptibility, sulbactam
|How to cite this article:|
Chiang TT, Tang HJ, Chiu CH, Chen TL, Ho MW, Lee CH, Sheng WH, Yang YS. Antimicrobial activities of cefoperazone-sulbactam in comparison to cefoperazone against clinical organisms from medical centers in Taiwan. J Med Sci 2016;36:229-33
|How to cite this URL:|
Chiang TT, Tang HJ, Chiu CH, Chen TL, Ho MW, Lee CH, Sheng WH, Yang YS. Antimicrobial activities of cefoperazone-sulbactam in comparison to cefoperazone against clinical organisms from medical centers in Taiwan. J Med Sci [serial online] 2016 [cited 2019 May 24];36:229-33. Available from: http://www.jmedscindmc.com/text.asp?2016/36/6/229/196365
| Introduction|| |
Cefoperazone has a broad-spectrum activity against both Gram-positive cocci (GPCs) and Gram-negative bacteria (GNBs). , However, antimicrobial resistance developed through various mechanisms, including β-lactamases produced by GNBs in recent decades. , Sulbactam has been shown to enhance the in vitro spectrum of cefoperazone, , and the combination is active against a great proportion of many clinical pathogens including multidrug-resistant GNBs (MDRGNBs).  These include extended-spectrum beta-lactamases (ESBLs) producing Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii.  Of noted, the sulbactam contained in this drug is also potentially active against A. baumannii,  which has become an emerging clinical pathogen. 
The antimicrobial susceptibilities of the microorganisms are crucial for the selection of appropriate antimicrobial therapy. Unfortunately, there were fewer data of the susceptibility of cefoperazone-sulbactam against commonly encountered clinical pathogens and the above-mentioned MDRGNBs in Taiwan recently. The most updated data were collected about 5 years ago.  Therefore, this study is conducted to evaluate the susceptibilities of cefoperazone-sulbactam in comparison to cefoperazone against various clinical isolates collected from medical centers in Taiwan.
| Methods|| |
The clinical isolates were collected from five medical centers in Taiwan, including Lin Kou Chang Gung Memorial Hospital and Taipei Veterans General Hospital in the north; China Medical University Hospital in the middle region; and Chi Mei Hospital and Kaohsiung Chang Gung Memorial Hospital in the south [Table 1].
Isolates were collected from various clinical specimens from five centers in 2012, which included Group A and B Streptococcus, Streptococcus pneumoniae, methicillin-susceptible Staphylococcus aureus (MSSA), Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis, P. aeruginosa, and A. baumannii [Table 1].
Antimicrobial susceptibility tests
The agar dilution method was performed in accordance with the guidance of Clinical and Laboratory Standards Institute (CLSI).  The combination ratio of cefoperazone and sulbactam for tests was 1:1.  Sulbactam combined with cefoperazone in a 1:1 ratio was purchased from TTY Biopharm, Taiwan.
The susceptibility breakpoints for cefoperazone-sulbactam are not elucidated in the current CLSI guidelines; hence, the CLSI breakpoint criteria  for cefoperazone alone were applied for cefoperazone-sulbactam for comparison purpose only. E. coli ATCC 25922 and 35218, P. aeruginosa ATCC 27853 were used as control strains.
To assess differences, the Chi-square test with Yate's correction or Fisher's exact test was used. A P < 0.05 was considered statistically significant. All the analyses were processed with Statistical Package for the Social Sciences software version 18.0 (SPSS, Chicago, IL, USA).
| Results|| |
A total of 476 GPC and 1796 GNB clinical isolates were collected. These included Group A Streptococcus (1.71%), Group B Streptococcus (4.48%), S. pneumoniae (3.82%), MSSA (10.65%), E. coli (11.00%), K. pneumoniae (10.17%), E. cloacae (7.83%), S. marcescens (5.37%), P. mirabilis (7.66%), P. aeruginosa (7.83%), Stenotrophomonas maltophilia (3.83%), Salmonella spp. (6.56%), and A. baumannii (16.51%). Antimicrobial susceptibilities of cefoperazone alone and in combination with sulbactam against GPCs are shown in [Table 2] and those against GNBs are shown in [Table 3]. Cefoperazone exhibited potent activity against most Streptococcus spp. and MSSA. In GNBs, cefoperazone had limited activity against most Enterobacteriaceae and nonfermenting GNBs. The overall susceptibilities of cefoperazone against important GNBs, including E. coli, K. pneumoniae, E. cloacae, P. mirabilis, P. aeruginosa, and other Enterobacteriaceae, were ranging from 5.8% to 76.4%. However, the susceptibilities against A. baumannii and S. maltophilia were low: 0.27% and 5.8%, respectively.
|Table 2: Antimicrobial susceptibilities of cefoperazone and cefoperazone-sulbactam against Gram-positive bacteria|
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|Table 3: Antimicrobial susceptibilities of cefoperazone and cefoperazone-sulbactam against Gram-negative bacteria|
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The combination of sulbactam and cefoperazone showed better activity against various GNBs tested compared to cefoperazone alone [Table 3]. In addition, the combination also exhibited better activity against A. baumannii than cefoperazone alone (71.2% vs. 0.27%).
The susceptibilities of cefoperazone-sulbactam against MDRGNBs are shown in [Table 4]. In ESBL-producing E. coli and ESBL-producing K. pneumoniae, the susceptibilities were 65.9% and 60.7%. And those against carbapenem-resistant A. baumannii and P. aeruginosa were 62.2% and 0%.
|Table 4: Antimicrobial susceptibilities of cefoperazone and cefoperazone-sulbactam against multidrug-resistant Gram-negative bacteria|
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| Discussion|| |
This study demonstrated the antimicrobial susceptibilities of cefoperazone alone and in combination of sulbactam against various clinical pathogens. Cefoperazone-sulbactam showed great activities against those commonly encountered clinical pathogens. In MDRGNBs, especially Enterobacteriaceae, P. aeruginosa, and A. baumannii isolates, cefoperazone-sulbactam demonstrated good antimicrobial activities, except those were carbapenem resistant and which may provide another therapeutic option for treating MDRGNBs.
In recent years, the emergence of antimicrobial resistance has become a worldwide problem. ESBL-producing Enterobacteriaceae, P. aeruginosa, and A. baumannii are frequently encountered MDRGNBs. In Taiwan, the annual prevalence rate of ESBL-producing E. coli and K. pneumoniae isolates doubled from 2008 to 2010 (5.2%-11.5%, and 4.5%-12.1%, respectively). , This significantly limited the choice of antimicrobial agents. Carbapenems were regarded as one of very limited choices for treating ESBL-producing Enterobacteriaceae infection. , In the current result, cefoperazone-sulbactam exhibited good activity against most Enterobacteriaceae, including those ESBL-producing strains. In addition, P. aeruginosa and Acinetobacter spp. are common pathogens of hospital-acquired infections, which are frequently resistant to multiple antibiotics. Recently, the antimicrobial resistance of P. aeruginosa was increasing including carbapenems.  The overall susceptibility of P. aeruginosa to cefepime, piperacillin-tazobactam, and imipenem was 71%, 83.9%, and 74.7%, respectively.  Furthermore, A. baumannii complex even exhibited higher resistances to cefepime, piperacillin-tazobactam, and imipenem, ranging from 58% to 68% (60.9%, 68.4%, and 58.7%, respectively).  In the current study, cefoperazone-sulbactam demonstrated good activity against P. aeruginosa and A. baumannii complex. By the irreversibly block the effects of several β-lactamases, cefoperazone-sulbactam also showed good activities against ESBLs such as TEM, SHV, and CTX-M.  The addition of sulbactam makes the full potential of cefoperazone to against Pseudomonas species and Enterobacteriaceae, even encountered those harboring plasmid-mediated transferable enzymes and extended-spectrum enzymes. 
In comparison to other countries of Asia-pacific region, cefoperazone-sulbactam exhibited better activities against those MDRGNBs in Taiwan, except for carbapenem-resistant P. aeruginosa and A. baumannii complex.,, In recent published data, the antimicrobial resistances of cefoperazone-sulbactam to E. coli and K. pneumoniae ranged from 2% to 35% and 4% to 17% in Asian countries other than Taiwan. ,, The ESBL producers ranged 9.7%-59.9% and 9.6%-61.3% among E. coli and K. pneumoniae isolates in Asia-pacific region. ,, The resistances of cefoperazone-sulbactam to those ESBL-producing E. coli and K. pneumoniae ranged 3.3%-71% and 8.6%-28.8%. ,,, The resistances of cefoperazone-sulbactam to P. aeruginosa and A. baumannii complex ranged 11.7%-24.2% and 26.3%-50%, respectively. ,,, As the emerging prevalence of carbapenem-resistant P. aeruginosa and A. baumannii complex ranging 10.4%-56.9% and 22.2%-86.7% among all those isolates, ,,, the resistances of cefoperazone-sulbactam to those carbapenem-resistant isolates mentioned above were even higher: 55.3%-69.8%. ,,,
| Conclusion|| |
Cefoperazone-sulbactam is active against most commonly encountered clinical pathogens in Taiwan. Moreover, it is active against MDR pathogens, such as ESBL-producing E. coli and K. pneumoniae and part of carbapenem-resistant A. baumannii complex, which can be a potentially therapeutic agent for treating infections caused by these pathogens.
Financial support and sponsorship
This work was supported by grants from the Tri-Service General Hospital (TSGH-C103-125, TSGH-C104-119, TSGH-105-113, and DV104-09), the Ministry of Science and Technology (103-2314-B-016-039 and 104-2314-B-016-051), Taiwan.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]