• Appendicitis (complicated by rupture or abscess) and peritonitis: Due to piperacillin-resistant, -lactamase producing strains of E.coli or these members of the Bacteroides group:B. fragilis, B. thetaiotaomicron, or B. vulgatus.
• Uncomplicated and complicated skin and skin structured infections: Those including cellulitis, cutaneous and ischemic/diabetic foot infections caused by piperacillin-resistant, -lactamse producing strains of S.aureus.
• Postpartum endometritis or pelvic inflammatory disease: Due to piperacillin-resistant, -lactamase producing strains of E.coli.

• Community-acquired pneumonia(moderate severity only): Due to piperacillin-resistant, -lactamase producing strains of H. influenzae.

• Nosocomial pneumonia(moderate to severe):Due to piperacillin-resistant,-lactamase producing strains of S.aureus.

 

The treatment of mixed infections caused by piperacillin-susceptible organisms and piperacillin- resistant,-lactamase producing organisms susceptible to piperacillin/tazobactam should not require adding another antibiotic. An exception is in the treatment of Pseudomonas aeruginosa in nosocomial pneumonia, which should be in combination with an aminoglycoside.

• Nosocomial pneumonia: Start with 3.375g every 4 hours plus an aminoglycoside. The recommended duration of treatment is 7 to 14 days. Continue the aminoglycoside in patients from whom P aeruginosa is isolated. If it is isolated, the aminoglycoside may be discontinued at the discretion of the treating physician as guided by the severity of the infection and the patient’s clinical and bacteriological progress.

• Renal function impairment: In patients with renal insufficiency (Creatinine Clearance<90ml/min) adjust the IV dose of the degree of actual renal function impairment. In patients with nosocomial pneumonia receiving concomitant aminoglcoside therapy, adjust the aminoglycoside dosage acoording to the manufacture’s recommendation

 

ZIFAM PTZ Dosage Recommendation
Creatinine clearance(ml/min)	Recommended dosage regimen
20-80	12g/1.5g/day in divided doses of 4.5g every 8 hours
<20	8g/1g/day in divided doses of 4.5g every 12 hours

 

• Hemodialysis: The maximum dose is 2.25 g every 8 hours. In addition because hemodialysis remove 30% to 40% of a dose in 4 hours, give one additional 0.75g dose following each dialysis period. Peritoneal dialysis removes 6% and 21% of the piperacillin and tazobactam doses respectively.
• Duration of Therapy: Continue administration for a minium 48 to 72 hours after fever abates or after evidence of bacterial eradication has been obtained. A minimum of 10 days treatment is recommended for grop A- hemolytics stertococcal infections to guard against the risk of rheumatic fever or glomerulonephritis. However, the recommended duration of ZIFAM PTZ treatment for nosocomial pneumonia is 7 to 14 days. In all conditions, the duration of therapy should be guided by the severity of the infection and the patient’s clinical and bacteriological progress.
• Intravenous Administration: For conventional vials, reconstitute ZIFAM PTZ 1 gram of piperacillin with 5ml of a compatible reconstitution diluent(given below)

• Compatible IV diluent solution: These include 0.9% Sodium Chloride for injection, Sterile Water for Injection(maximum recommended volume per dose is 50ml), Dextrose 5%, Dextran 6% in Saline.

 

Storage/Stability: Reconstitute conventional vials with 5 ml of compatible diluent per gram of piperacillin. Shake well until dissolved. Use single dose via immediately after reconstitution. Discard any unused portion after 24 hours at room temperature and up to one week.

• at refrigerated temperature. Stability in an ambulatory IV infusion pump has been demonstrated for a period of 12 hours at room temperature.

Before initiating therapy with ZIFAM PTZ, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, ZIFAM PTZ should be discontinued and appropriate therapy instituted.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including piperacillin/tazobactam, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of “antibiotic-associated colitis”.

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

If bleeding manifestations occur, ZIFAM PTZ should be discontinued and appropriate therapy instituted.

As with other penicillins, patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given intravenously (particularly in the presence of renal failure).

ZIFAM PTZ is a monosodium salt of piperacillin and a monosodium salt of tazobactam and contains a total of 2.35mEq(54mg) of Na+ per gram of piperacillin in the combination product. This should be considered when treating patients requiring restricted salt intake. Periodic electrolyte determinatios should be performed in patients with low potassium reserves, and the possibility of hypokalemia should be kept in mind with patients who have potentially low potassium reserves and who are receiving cytotoxic therapy or diuretics.

The possibility of the emergence of resistant organisms that might cause superinfections shuld be kept in mind.

As with other semisynthetic penicillins, piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.

Cardiovascular– tachycardia, including supraventricular and ventricular; bradycardia; arrhythmia, including atrial fibrillation, ventricular filbrillation, cardiac arrest, cardiac failure, circulatory failure, myocardial infarction angina.

Central nervous system- tremor, ocnvulsions, vertigo, aggressive reaction (combative).

Gastrointestinal – melena, flatulence, hemorrhage, gastritis, hiccough, ulcerative stomatitis, fecal incontinence, gastric ulcer, pancreatitis.

Pseudomembranouls colitis was reported in one patient during the clinical trials. The onset of pseudomembranous coliits symptoms may occur during or after antibacterial tretment.

Hearing and Vestibular System- tinnitus, deafness, earache

Hypersensitivity- anaphylaxis

Metabolic and Nutritional– symptomatic hypoglycemia, thirst, gout, vitamin B₁₂ deficiency anemia

Musculoskeletal – myalgia, arthralgia

Platelets, Bleeding, Clotting – mesenteric embolism, purpura, epistaxis, pulmonary embolism, ecchymosis, hemoptysis

Psychiatirc– confusion, hallucination, depression

Reproductive, Female – leukorrhea, vaginitis perineal irritation/pain

Respiratory– pharyngiits, pulmonary edema, bronchospasm, coughing, atelectasis, dyspnea, hypoxia

Skin and Appendages- genital pruitus, diaphoresis, conjunctivitis, xerosis

Special senses– taste perversion

Urinary- retention, dysuria, oliguria, hematuria, incontinence, urinary tract infection with trichomonas, yeast in urine

Vision- photophobia

Vascular (extracardiac)- flushing cardiovascular accident

Additional adverse events reported from worldwide marketing experience with Piperacillin and tazobactam for injection, occurring under circumstances where casual relationship to ZIFAM PTZ is uncertain;

Gastrointestinal- hepatitis, cholestatic jaundice

Hematologic- hemolytic anemia

Renal-rarely, interstitial nephritis

Excessive serum concentrations of either piperacillin or tazobactam may be reduced by hemodialysis. No specific antidotes is known. As with other penicillins, neuromuscular excitability or convulsions have occurred following large intravenous doses, primarily in patients with impaired renal function. In the case of motor excitability or convulsions, general supportie measures, including administration of anitconvulsive agents (e.g. diazepam or barbiturates), may be considered.