Cefoperazone-sulbactam for treatment of intra-abdominal infections: results from a randomized, parallel group study in India.
BACKGROUND
Combinations of a third-generation cephalosporin and metronidazole, with or without an aminoglycoside, often are used for the treatment of intra-abdominal infections in surgical settings. Simpler regimens that preserve an adequate spectrum of coverage, but allow easier administration and have fewer side effects, may be a more desirable option.


METHODS
This randomized, open-label, active comparator study evaluated the effectiveness (non-inferiority hypothesis) of the beta-lactam/beta-lactamase inhibitor combination cefoperazone-sulbactam (2-8 g/day), compared with ceftazidime (2-6 g/day)-amikacin (15 mg/kg/day)-metronidazole (500 mg three times daily) in 154 and 152 subjects, respectively, having intra-abdominal infections. The study was conducted at 17 centers in India.


RESULTS
Non-inferiority of cefoperazone-sulbactam (91.9%) compared with ceftazidime-amikacin-metronidazole (81.8%) was demonstrated for continued resolution of clinical signs and symptoms at the 30-day follow-up (primary endpoint) with a treatment difference of 10.1% (95% confidence interval 2.1%, 18.1%; pre-defined non-inferiority limit > -12.5%). Superiority of cefoperazone-sulbactam also was demonstrated for this endpoint, with significantly more subjects achieving continued resolution at the 30-day follow-up than in the comparator group (p = 0.015). On microbiologic outcomes, cefoperazone-sulbactam had higher success rates than ceftazidime-amikacin-metronidazole (92.9% vs. 80.0%). The pathogens (202 isolated) isolated most commonly were Escherichia coli (38.6%) and Klebsiella spp. (12.9%). The incidence of treatment-related adverse events was 6.5% and 16.4% in the cefoperazone-sulbactam and ceftazidime-amikacin-metronidazole groups, respectively, with more discontinuations due to treatment-related adverse events in the comparator arm (3.2% vs. 9.9%).


CONCLUSIONS
Empirical cefoperazone-sulbactam monotherapy could be a useful adjunct to surgical intervention for intra-abdominal infections.
King George Medical University, Lucknow, India.
Abhijit
A
Chandra
Puneet
P
Dhar
Satish
S
Dharap
Amitabh
A
Goel
Rajesh
R
Gupta
Jayprakash V
JV
Hardikar
Vinay K
VK
Kapoor
Ashok K
AK
Mathur
Pankaj
P
Modi
Mahendra
M
Narwaria
Mayakonda K
MK
Ramesh
Hariharan
H
Ramesh
R A
RA
Sastry
Shashank
S
Shah
Satpalsingh
S
Virk
Otivilvayoth V
OV
Sudheer
Maddibande R
MR
Sreevathsa
Subodh
S
Varshney
Puja
P
Kochhar
Sanjay
S
Somasundaram
Chetan
C
Desai
Manjula
M
Schou
D018784:Abdominal Abscess / Q000188:drug therapy* / Q000382:microbiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000583:Amikacin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002438:Cefoperazone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002442:Ceftazidime / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007194:India; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology; D013407:Sulbactam / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D008795:Metronidazole; D002438:Cefoperazone; D000583:Amikacin; D002442:Ceftazidime; D013407:Sulbactam