Septicemia
4. Meningitis
5. Skin & Soft tissue infection
6. Endometritis
7. Other infection of genital tract
8. Intraabdominal infection
9. Bone & joint infection

The drug should be discontinued and the appropriate therapy instituted if an allergic reaction occurs. Anaphylactic serious reactions require immediate emergency treatment with epinephrine. Intravenous steroids, oxygen, and airway management, including intubation, should be administered as indicated.
• Use in Hepatic Dysfunction
Cefoperazone is extensively excreted in bile. In patients with hepatic diseases and/or biliary obstruction the serum half-life of cefoperazone is usually prolonged and urinary excretion of the drug increased. Even with severe hepatic dysfunction, therapeutic concentrations of cefoperazone are obtained in bile and only a 2 – 4 fold increase in half-life is seen. In cases of severe biliary obstruction, severe hepatic disease or in cases of renal dysfunction coexistent with either of those conditions dose modification may be necessary. Cefoperazone serum concentrations should be monitored and dosage adjusted as necessary in patients with hepatic dysfunction and concomitant renal impairment. In such cases dosage should not exceed 2 g/day of cefoperazone without close monitoring of serum concentrations.
• General
As with other antibiotics, in a few patients treated with cefoperazone Vitamin K deficiency has occurred. The mechanism is most probably associated to the suppression of gut flora which normally synthesize this vitamin. Those at risk include patients on prolonged intravenous alimentation regimens and patients with poor diet, malabsorption states (e.g., cystic fibrosis). In these patients, and patients receiving anticoagulant therapy, and exogenous vitamin K administered as indicated prothrombin time should be monitored. Overgrowth of nonsusceptible organisms may occur during prolonged use of sulbactam/cefoperazone as with other antibiotics. Patients should be observed carefully during treatment. As with any potent systemic agent, it is advisable to check periodically for organ system dysfunction during extended therapy; this includes hematopoietic and renal hepatic systems. This is important particularly in neonates, especially when premature, and other infants.
• Use In Infancy
In infants Sulbactam/cefoperazone has been used effectively. In premature infants or neonates it has not been extensively studied. Therefore, potential benefits and possible risks involved should be considered before instituting therapy in treating premature infants and neonates.
• Clostridium difficile associated diarrhea (CDAD):
CDAD has been reported with use of antibacterial agents, including sulbactam sodium/cefoperazone sodium, and may range in severity from mild diarrhea to fatal colitis. Normal flora of the colon is altered by treatment with antibacterial agents leading to overgrowth of C difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased mortality and morbidity, as these infections can be refractory to antimicrobial therapy and may require colectomy. Subsequent to antibiotic use , CDAD must be considered in all patients who present with diarrhea. Since CDAD has been reported to occur over two months after the administration of antibacterial agents careful medical history is necessary. Cefoperazone does not displace bilirubin from plasma protein binding sites.

• Miscellaneous – Headache, fever, injection pain and chills
• Laboratory Abnormalities – Transient elevations of liver function tests, SGOT 5.7% , SGPT 6.2%, alkaline phosphatase 2.4% and bilirubin 1.2% levels, have been noted.
• Local Reactions – transient pain, phlebitis at the infusion site.
• In post-marketing experience – General: anaphylactoid reaction (including shock)
Cardiovascular: hypotension
Gastrointestinal: pseudomembranous colitis
Hematopoietic: leucopenia
Skin/Appendages: pruritus, Stevens Johnson Syndrome
Urinary: hematuria
Vascular: vasculitis.

Consideration should be given to neurologic effects, including seizures that may be caused by high CSF concentrations of β-lactam antibiotics. Because cefoperazone and sulbactam are removed from the circulation by hemodialysis, these procedures may enhance elimination of the drug from the body in patients with impaired renal function if overdosage occurs.

Sulbactam does not possess any useful antibacterial activity, except against Acinetobacter and Neisseriaceae
However, biochemical studies with cell-free bacterial systems have shown it as irreversible inhibitor of most important beta-lactamases that is produced by beta-lactam antibiotic-resistant organisms.
The potential for sulbactam’s preventing the destruction of penicillins and cephalosporins by resistant organisms was reported in whole-organism studies with resistant strains in which sulbactam exhibited marked synergy with penicillins and cephalosporins.
Sensitive strains are also often rendered more susceptible to sulbactam/cefoperazone than to cefoperazone alone, as sulbactam also binds with some penicillin binding proteins. The combination of cefoperazone and sulbactam is active against all organisms sensitive to cefoperazone. Pharmacokinetic Properties