piperacillin

Piperacillin is a semisynthetic extended-spectrum antibiotic of the penicillin group of antibiotics. Extended spectrum penicillins are penicillin antibiotics chemically altered to make them effective against a wider spectrum of bacteria. Piperacillin is administered as an intravenous (IV) or intramuscular (IM) injection and is used to treat various types of serious infections caused by susceptible strains of bacteria. Piperacillin is often used in combination with tazobactam, another type of antibiotic.

Piperacillin binds to penicillin binding proteins on the inner membrane of the bacterial cell wall and prevents the cross-linking of peptidoglycan chains, which is necessary for maintaining the integrity and strength of the cell wall. This results in the weakening of the bacterial cell wall and leakage of its contents, leading to death of the bacteria.

Piperacillin is effective against many aerobic and anaerobic gram-positive and gram-negative bacteria. Aerobic bacteria require oxygen to survive, while anaerobic bacteria thrive in tissue that lacks oxygen. Gram-negative and gram-positive bacteria are structurally different, and the two types are identified by whether the bacteria get dyed or not in the Gram stain lab test.

Piperacillin is used to treat the following infections:

• Intra-abdominal infections
• Urinary tract infections
• Gynecologic infections
• Septicemia
• Lower respiratory tract infections
• Skin and skin structure infections
• Bone and joint infections
• Uncomplicated gonococcal urethritis

Piperacillin is used to prevent infections from surgical procedures including:

• Intra-abdominal (gastrointestinal and biliary) procedures
• Vaginal hysterectomy
• Abdominal hysterectomy
• Cesarean section

Organisms susceptible to piperacillin include:

Aerobic gram-positive microorganisms

• Enterococci, including Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes

Aerobic gram-negative microorganisms

• Acinetobacter species, Enterobacter species, Escherichia coli, Haemophilus influenzae (non-beta-lactamase-producing strains), Klebsiella species, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Serratia species

Anaerobic gram-positive microorganisms

• Anaerobic cocci, Clostridium species

Anaerobic gram-negative microorganisms

• Bacteroides species, including Bacteroides fragilis

• Do not use to treat patients with a history of allergic reactions to penicillins, cephalosporins, piperacillin or any of its components.
• There have been reports of serious allergic reactions (anaphylactic/anaphylactoid) in patients treated with penicillin antibiotics. If an allergic reaction occurs, discontinue piperacillin immediately and institute appropriate treatment.
• Piperacillin can cause Clostridium difficile associated diarrhea (CDAD) that may range from mild diarrhea to fatal colitis. Surgical removal of affected portions of colon (colectomy) may be required in some cases.
• Consider possibility of clostridium difficile in all patients who present with diarrhea following antibiotic use. In case of suspected or confirmed CDAD:
  • All antibiotics excluding those directed against C. difficile must be stopped
  • Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted
• Piperacillin treatment may affect blood clotting function and there have been incidences of bleeding. Monitor patients and if bleeding manifestations occur, discontinue the drug and initiate appropriate treatment.
• Piperacillin formulation contains sodium. Use with caution in patients on sodium-restricted diet and monitor electrolyte levels and cardiac function in patients receiving prolonged treatment.
• Use with caution in patients with impaired kidney function because of the sodium load. Dosage adjustment may be required.
• Monitor liver and kidney function, especially with prolonged treatment.
• Prolonged therapy may cause leukopenia and neutropenia.
• Patients may experience neuromuscular excitability or convulsions with higher than recommended IV doses. Use with caution in patients with a history of seizures.
• Piperacillin has been associated with an increased incidence of fever and rash in cystic fibrosis patients.
• Treatment with other penicillins has led to development of rash in patients with mononucleosis.
• Symptoms of syphilis may be masked or delayed in patients receiving high-dose antimicrobial treatment for gonorrhea. Evaluate patients for syphilis before starting piperacillin and if syphilis is suspected, continue testing every month for 4 months.
• Piperacillin treatment may lead to superinfections of resistant organisms, particularly with prolonged therapy.
• In the absence of a proven or strongly suspected bacterial infection or a prophylactic indication, piperacillin is unlikely to be beneficial and increases the risk of development of drug-resistant bacteria.

Common side effects of piperacillin include:

• Local reactions at the administration site including:
  • Blood clot with inflammation in the vein (thrombophlebitis)
  • Pain
  • Redness (erythema)
  • Hardening of tissue (induration)
  • Discoloration from bleeding under the skin (ecchymosis)
  • Hematoma
  • Deep vein thrombosis (DVT)
• Diarrhea
• Loose stools
• Nausea
• Vomiting
• Bloody diarrhea
• Pseudomembranous colitis, colon inflammation due to Clostridium difficile bacteria overgrowth
• Elevation in liver enzymes LDH, AST and ALT
• High level of bilirubin in blood (hyperbilirubinemia)
• Liver inflammation due to impaired bile flow (cholestatic hepatitis)
• Elevation of creatinine level in blood
• Increase in blood urea nitrogen (BUN)
• Inflammation in the kidneys (interstitial nephritis)
• Kidney failure
• Electrolyte disturbance
• Low blood potassium levels (hypokalemia)
• Dizziness
• Headache
• Fatigue
• Seizures
• Prolonged muscle relaxation
• Fever
• Superinfections including Candida yeast infection
• Hypersensitivity reactions including severe allergic reaction (anaphylaxis)
• Skin reactions including:
  • Rash
  • Hives (urticaria)
  • Itching (pruritus)
  • Fluid-filled blisters (vesicular eruptions)
  • Erythema multiforme
  • Toxic epidermal necrosis
  • Stevens-Johnson syndrome
• Presence of antibodies against red blood cells (positive Coombs test)
• Increased incidence of fever and rash in patients with cystic fibrosis 
• Blood disorders including:
  • Low red blood cell count due to rapid destruction (hemolytic anemia)
  • Severely low count of granulocyte immune cells (agranulocytosis)
  • Low count of neutrophil immune cells (neutropenia)
  • Low count of leukocyte immune cells (leukopenia), usually with prolonged treatment with high doses (reversible)
  • Low platelet count (thrombocytopenia)
  • Low count of all types of blood cells (pancytopenia)
  • High eosinophil count (eosinophilia)
  • Prolonged blood clotting time

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Powder for Injection

• 2 g
• 3 g
• 4 g
• 40 g

Adult:

Usual Dosage Range

• Intravenous (IV): 3-4 g/dose every 4-6 hours; not to exceed 24 g/24 hours
• Intramuscular (IM): 2-3 g/dose every 6-12 hours; not to exceed 24 g/24 hours

Urinary Tract, Uncomplicated

• 6-8 g/day IV/IM (100 to 125 mg/kg/day) divided every 6-12 hours 

Community-Acquired Pneumonia

• 6-8 g/day IV/IM (100 to 125 mg/kg/day) divided every 6-12 hours

Acute Cholangitis

• 4 g IV every 6 hours

Moderate Infections

• 2-3 g/dose IV/IM every 6-12 hours; not to exceed 2 g IM/site

Severe Infections

• 3-4 g IV/IM every 4-6 hours; not to exceed 24 g/24 hours

Uncomplicated Gonorrhea

2 g once with 1 g probenecid 30 minutes before injection

Pseudomonas Infections

• 4 g IV/IM every 4 hours

Renal Impairment

Creatinine clearance (CrCl) 20-40 mL/min: 3-4 g every 8 hours

CrCl below 20 mL/min: 3-4 g every 12 hours

Geriatric:

• Adjust dose for renal impairment

Usual dosage range

• IV: 2-4 g every 6-8 hours
• IM: 1-2 g every 8-12 hours

Pediatric:

Usual Dosage Range

• Neonates: 100 mg/kg IV/IM every 12 hours  
• Infants and Children: 200-300 mg/kg/day IV/IM divided every 4-6 hours

Cystic Fibrosis

• 350-500 mg/kg/day IV/IM divided every 4-6 hours 

Overdose

• There is no specific information on piperacillin overdose, however, overdose of other penicillin class of drugs can cause neuromuscular hyperirritability or convulsive seizures.
• Overdose treatment includes discontinuation of piperacillin, and symptomatic and supportive care as required.
• Piperacillin can be removed by hemodialysis but not peritoneal dialysis.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Piperacillin has no known severe interactions with other drugs.
• Serious interactions of piperacillin include:
  • antithrombin alfa
  • antithrombin III
  • argatroban
  • BCG vaccine live
  • bivalirudin
  • cholera vaccine
  • dalteparin
  • enoxaparin
  • heparin
  • omadacycline
  • sarecycline
• Moderate interactions of piperacillin include:
  • azithromycin
  • bazedoxifene/conjugated estrogens
  • chloramphenicol
  • clarithromycin
  • demeclocycline
  • dichlorphenamide
  • doxycycline
  • erythromycin base
  • erythromycin ethylsuccinate
  • erythromycin lactobionate
  • erythromycin stearate
  • minocycline
  • probenecid
  • sodium picosulfate/magnesium oxide/anhydrous citric acid
  • tetracycline
  • vancomycin
  • vecuronium
  • warfarin
• Mild interactions of piperacillin include:
  • amikacin
  • aspirin
  • aspirin rectal
  • aspirin/citric acid/sodium bicarbonate
  • chlorothiazide
  • choline magnesium trisalicylate
  • gentamicin
  • hydrochlorothiazide
  • ibuprofen IV
  • meclofenamate
  • neomycin PO
  • rose hips
  • streptomycin
  • tobramycin
  • willow bark

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or healthcare provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• Animal reproductive studies do not show evidence of fetal harm, however, there are no adequate and well-controlled studies on the safety of piperacillin use in pregnant women. Use piperacillin during pregnancy only if it is clearly needed.
• Piperacillin is excreted in breast milk in low concentrations. Use with caution in nursing mothers.

• Complete the prescribed antibiotic therapy, do not skip your appointment for injections or discontinue therapy if you feel better. It can decrease effectiveness of treatment and can also lead to development of drug-resistant bacteria.
• Diarrhea is a common problem with antibiotic treatments which should resolve with the completion of the therapy. Notify your physician immediately if you have watery or bloody stools, with or without stomach cramps and fever. Symptoms can develop even up to two months after the last dose of antibiotic.
• Inform your physician immediately if you develop hypersensitivity reactions such as rash or severe allergic reactions including breathing difficulties.
• Contact your physician or Poison Control if you suspect an overdose.