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Zosyn Disease Interactions

There are 8 disease interactions with Zosyn (piperacillin / tazobactam).


Antibiotics (applies to Zosyn) colitis

Major Potential Hazard, Moderate plausibility. Applicable conditions: Colitis/Enteritis (Noninfectious)

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.


  1. (2002) "Product Information. Omnipen (ampicillin)." Wyeth-Ayerst Laboratories
  2. (2002) "Product Information. Ceftin (cefuroxime)." Glaxo Wellcome
  3. (2002) "Product Information. Zinacef (cefuroxime)." Glaxo Wellcome
  4. (2002) "Product Information. Cleocin (clindamycin)." Pharmacia and Upjohn
  5. (2002) "Product Information. Macrobid (nitrofurantoin)." Procter and Gamble Pharmaceuticals
  6. (2002) "Product Information. Macrodantin (nitrofurantoin)." Procter and Gamble Pharmaceuticals
  7. (2001) "Product Information. Amoxil (amoxicillin)." SmithKline Beecham
  8. (2001) "Product Information. Merrem (meropenem)." Astra-Zeneca Pharmaceuticals
  9. (2001) "Product Information. Coly-Mycin M Parenteral (colistimethate)." Parke-Davis
  10. (2001) "Product Information. Lincocin (lincomycin)." Pharmacia and Upjohn
  11. (2003) "Product Information. Cubicin (daptomycin)." Cubist Pharmaceuticals Inc
  12. (2004) "Product Information. Xifaxan (rifaximin)." Salix Pharmaceuticals
  13. (2007) "Product Information. Doribax (doripenem)." Ortho McNeil Pharmaceutical
  14. (2009) "Product Information. Penicillin G Procaine (procaine penicillin)." Monarch Pharmaceuticals Inc
  15. (2009) "Product Information. Vibativ (telavancin)." Theravance Inc
  16. (2010) "Product Information. Teflaro (ceftaroline)." Forest Pharmaceuticals
  17. (2022) "Product Information. Penicillin G Sodium (penicillin G sodium)." Sandoz Inc
  18. (2014) "Product Information. Dalvance (dalbavancin)." Durata Therapeutics, Inc.
  19. (2014) "Product Information. Orbactiv (oritavancin)." The Medicines Company
  20. (2017) "Product Information. Bicillin C-R (benzathine penicillin-procaine penicillin)." A-S Medication Solutions
  21. (2017) "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc.
  22. (2022) "Product Information. Polymyxin B Sulfate (polymyxin B sulfate)." AuroMedics Pharma LLC
  23. (2018) "Product Information. Zemdri (plazomicin)." Achaogen
  24. (2018) "Product Information. Seysara (sarecycline)." Allergan Inc
  25. (2018) "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc.
  26. (2018) "Product Information. Aemcolo (rifamycin)." Aries Pharmaceuticals, Inc.
  27. (2019) "Product Information. Fetroja (cefiderocol)." Shionogi USA Inc
  28. (2019) "Product Information. Biaxin (clarithromycin)." AbbVie US LLC, SUPPL-61
  29. (2021) "Product Information. Zithromax (azithromycin)." Pfizer U.S. Pharmaceuticals Group, LAB-0372-7.0
  30. (2018) "Product Information. E.E.S.-400 Filmtab (erythromycin)." Arbor Pharmaceuticals, SUPPL-74
  31. (2020) "Product Information. Priftin (rifapentine)." sanofi-aventis, SUPPL-18
  32. (2021) "Product Information. Xerava (eravacycline)." Tetraphase Pharmaceuticals, Inc
  33. (2023) "Product Information. Xacduro (durlobactam-sulbactam)." La Jolla Pharmaceutical
  34. (2024) "Product Information. Exblifep (cefepime-enmetazobactam)." Allecra Therapeutics
  35. (2021) "Product Information. Maxipime (cefepime)." Hospira Inc, SUPPL-46
View all 35 references

Antipseudomonal PCNs (applies to Zosyn) coagulation abnormalities

Moderate Potential Hazard, Low plausibility. Applicable conditions: Bleeding, Coagulation Defect, Renal Dysfunction, Thrombocytopathy, Thrombocytopenia, Vitamin K Deficiency

The use of extended-spectrum penicillin antibiotics has rarely been associated with coagulation abnormalities manifested as prolonged prothrombin and bleeding times, abnormal platelet aggregation, purpura, and clinical bleeding. These reactions have been most severe and most frequently reported in patients with renal impairment given high dosages of the drugs for prolonged periods, although they have also occurred with usual dosages in patients with normal renal function. Therapy with extended-spectrum penicillins should be administered cautiously in patients with significantly impaired renal function, severe active bleeding, or a hemorrhagic diathesis such as hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, or thrombocytopathy. Clinical monitoring of hematopoietic and renal function is recommended during prolonged and/or high-dose therapy. Bleeding manifestations are reversible upon discontinuation of the antibiotic.


  1. Lutz B, Mogabgab W, Holmes B, et al. (1982) "Clinical evaluation of the therapeutic efficacy and tolerability of piperacillin." Antimicrob Agents Chemother, 22, p. 10-4
  2. Eliopoulos GM, Moellering RC (1982) "Azlocillin, mezlocillin, and piperacillin: new broad-spectrum penicillins." Ann Intern Med, 97, p. 755-60
  3. Moore M, McNamara TR, Johnson J (1985) "Elevated bleeding time and epistaxis associated with piperacillin therapy." South Med J, 78, p. 363
  4. Lee M, Stobnicki M, Sharifi R (1986) "Hemorrhagic complications of piperacillin therapy." J Urol, 136, p. 454-5
  5. Fass RJ, Copelan EA, Brandt JT, Moeschberger ML, Ashton JJ (1987) "Platelet-mediated bleeding caused by broad-spectrum penicillins." J Infect Dis, 155, p. 1242-8
  6. Russo J, Russo ME (1982) "Comparative review of two new wide-spectrum penicillins: mezlocillin and piperacillin." Clin Pharm, 1, p. 207-16
  7. Konopka (1982) "Clinical experience with mezlocillin in Europe: an overview." J Antimicrob Chemother, 9, p. 1-6
  8. Parry MF, Neu HC (1982) "The safety and tolerance of mezlocillin." J Antimicrob Chemother, 9, p. 1-8
  9. Stuart JJ (1980) "Ticarcillin-induced hemorrhage in a patient with thrombocytosis." South Med J, 73, p. 1084-5
  10. Mehta P, Lawson D, Gross S, Graham-Pole J (1989) "Comparative effects of mezlocillin and carbenicillin on platelet function and thromboxane generation in patients with cancer." Am J Pediatr Hematol Oncol, 11, p. 286-91
  11. Gentry LO, Jemsek JG, Natelson EA (1981) "Effects of sodium piperacillin on platelet function in normal volunteers." Antimicrob Agents Chemother, 19, p. 532-3
  12. (2002) "Product Information. Mezlin (mezlocillin)." Bayer
  13. (2001) "Product Information. Pipracil (piperacillin)." Lederle Laboratories
  14. (2001) "Product Information. Ticar (ticarcillin)." SmithKline Beecham
  15. Kuye O, Teal J, DeVries VG, Morrow CA, Tally FP (1993) "Safety profile of piperacillin/tazobactam in phase I and III clinical studies." J Antimicrob Chemother, 31, p. 113-24
  16. Gharpure V, Oconnell B, Schiffer CA (1993) "Mezlocillin-induced thrombocytopenia." Ann Intern Med, 119, p. 862
View all 16 references

Beta-lactamase inhibitors (applies to Zosyn) renal dysfunction

Moderate Potential Hazard, Moderate plausibility.

Beta-lactamase inhibitors are available in combination with beta-lactam antibacterial agents. Beta-lactamase inhibitors are primarily eliminated by the kidneys, with 75% to over 95% of the administered dose excreted as unchanged drug. The plasma exposures (AUC) of beta-lactamase inhibitors (and the associated beta-lactam antibacterial agents) are increased with decreasing renal function. Dosage adjustments are generally necessary for products containing beta-lactamase inhibitors, and modifications should be based on the degree of renal dysfunction in accordance with the individual manufacturer product information. Because it may change during the course of therapy, renal function should be monitored regularly and the dosage should be adjusted accordingly, as appropriate.

Beta-lactamase inhibitors and beta-lactam antibacterial agents can be removed by hemodialysis. The dose should be administered after hemodialysis on hemodialysis days.


  1. (2022) "Product Information. Zerbaxa (ceftolozane-tazobactam)." Merck Sharp & Dohme LLC, SUPPL-12
  2. (2022) "Product Information. Avycaz (avibactam-ceftazidime)." Forest Pharmaceuticals, SUPPL-11
  3. (2023) "Product Information. Xacduro (durlobactam-sulbactam)." La Jolla Pharmaceutical
  4. (2020) "Product Information. Recarbrio (imipenem/cilastatin/relebactam)." Merck Sharp & Dohme LLC, SUPPL-2
  5. (2022) "Product Information. Zosyn (piperacillin-tazobactam)." Baxter I.V. Systems Division, SUPPL-49
  6. (2020) "Product Information. Unasyn (ampicillin-sulbactam)." Pfizer U.S. Pharmaceuticals Group, SUPPL-47
  7. (2024) "Product Information. Exblifep (cefepime-enmetazobactam)." Allecra Therapeutics
View all 7 references

Beta-lactams (parenteral) (applies to Zosyn) renal dysfunction

Moderate Potential Hazard, Moderate plausibility.

Most beta-lactam antibacterial agents are eliminated by the kidney as unchanged drug and, in some cases, also as metabolites. The serum concentrations of beta-lactam antibacterial agents and their metabolites may be increased, and the half-lives prolonged, in patients with impaired renal function. Neurotoxic reactions (e.g., encephalopathy, aphasia, asterixis, myoclonus, seizures, nonconvulsive status epilepticus, coma) have been reported in such patients treated parenterally with these agents. Dosage adjustments may be necessary, and modifications should be based on the degree of renal function as well as severity of infection in accordance with the individual manufacturer product information. Renal function tests should be performed periodically during prolonged and/or high-dose therapy since nephrotoxicity and alterations in renal function have occasionally been associated with the use of these drugs.


  1. (2002) "Product Information. Omnipen (ampicillin)." Wyeth-Ayerst Laboratories
  2. (2002) "Product Information. Ancef (cefazolin)." SmithKline Beecham
  3. (2002) "Product Information. Zefazone (cefmetazole)." Pharmacia and Upjohn
  4. (2002) "Product Information. Monocid (cefonicid)." SmithKline Beecham
  5. (2002) "Product Information. Claforan (cefotaxime)." Hoechst Marion Roussel
  6. (2002) "Product Information. Cefotan (cefotetan)." Stuart Pharmaceuticals
  7. (2002) "Product Information. Mefoxin (cefoxitin)." Merck & Co., Inc
  8. (2002) "Product Information. Fortaz (ceftazidime)." Glaxo Wellcome
  9. (2002) "Product Information. Tazicef (ceftazidime)." SmithKline Beecham
  10. (2002) "Product Information. Cefizox (ceftizoxime)." Fujisawa
  11. (2002) "Product Information. Ceftin (cefuroxime)." Glaxo Wellcome
  12. (2002) "Product Information. Zinacef (cefuroxime)." Glaxo Wellcome
  13. (2002) "Product Information. Keflin (cephalothin)." Lilly, Eli and Company
  14. (2002) "Product Information. Cefadyl (cephapirin)." Apothecon Inc
  15. (2002) "Product Information. Staphcillin (methicillin)." Apothecon Inc
  16. (2001) "Product Information. Pfizerpen (penicillin)." Roerig Division
  17. (2001) "Product Information. Pipracil (piperacillin)." Lederle Laboratories
  18. (2001) "Product Information. Ticar (ticarcillin)." SmithKline Beecham
  19. (2001) "Product Information. Mandol (cefamandole)." Lilly, Eli and Company
  20. (2019) "Product Information. Fetroja (cefiderocol)." Shionogi USA Inc
  21. (2024) "Product Information. Exblifep (cefepime-enmetazobactam)." Allecra Therapeutics
  22. (2021) "Product Information. Maxipime (cefepime)." Hospira Inc, SUPPL-46
View all 22 references

Penicillins (applies to Zosyn) hemodialysis

Moderate Potential Hazard, High plausibility.

Penicillin antibiotics (except for agents in the penicillinase-resistant class) are removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.


  1. Giron JA, Meyers BR, Hirschman SZ, Srulevitch E (1981) "Pharmacokinetics of piperacillin in patients with moderate renal failure and in patients undergoing hemodialysis." Antimicrob Agents Chemother, 19, p. 279-83
  2. Heim KL (1985) "The effect of hemodialysis on piperacillin pharmacokinetics." Drug Intell Clin Pharm, 19, p. 455
  3. Francke EL, Appel GB, Neu HC (1979) "Kinetics of intravenous amoxicillin in patients on long-term dialysis." Clin Pharmacol Ther, 26, p. 31-5
  4. Slaughter RL, Kohli R, Brass C (1984) "Effects of hemodialysis on the pharmacokinetics of amoxicillin/clavulanic acid combination." Ther Drug Monit, 6, p. 424-7
  5. Janicke DM, Mangione A, Schultz RW, Jusko WJ (1981) "Mezlocillin disposition in chronic hemodialysis patients." Antimicrob Agents Chemother, 20, p. 590-4
  6. Kampf D, Schurig R, Weihermuller K, Forster D (1980) "Effects of impaired renal function hemodialysis and peritoneal dialysis on the pharmacokinetics of mezlocillin." Antimicrob Agents Chemother, 18, p. 81-7
  7. Davies BE, Boon R, Horton R, Reubi FC, Descoeudres CE (1988) "Pharmacokinetics of amoxycillin and clavulanic acid in haemodialysis patients following intravenous administration of augmentin." Br J Clin Pharmacol, 26, p. 385-90
  8. Francke E, Mehta S, Neu HC, Appel GB (1979) "Kinetics of intravenous mezlocillin in chronic hemodialysis patients." Clin Pharmacol Ther, 26, p. 228-31
  9. Thorsteinsson SB, Steingrimsson O, Asmundsson P, Bergan T (1981) "Pharmacokinetics of mezlocillin during haemodialysis." Scand J Infect Dis, 29, p. 59-63
  10. Wise R, Reeves DS, Parker AS (1974) "Administration of ticarcillin, a new antipseudomonal antibiotic, in patients undergoing dialysis." Antimicrob Agents Chemother, 5, p. 119-20
  11. Brogard JM, Comte F, Spach MO, Lavillaureix J (1982) "Pharmacokinetics of mezlocillin in patients with kidney impairment: special reference to hemodialysis and dosage adjustments in relation to renal function." Chemotherapy, 28, p. 318-26
  12. Oe PL, Simonian S, Verhoef J (1973) "Pharmacokinetics of the new penicillins." Chemotherapy, 19, p. 279-88
  13. Reitberg DP, Marble DA, Schultz RW, Whall TJ, Schentag JJ (1988) "Pharmacokinetics of cefoperazone (2.0 g) and sulbactam (1.0 g) coadministered to subjects with normal renal function, patients with decreased renal function, and patients with end-stage renal disease on hemodialysis." Antimicrob Agents Chemother, 32, p. 503-9
  14. Blum RA, Kohli RK, Harrison NJ, Schentag JJ (1989) "Pharmacokinetics of ampicillin (2.0 grams) and sulbactam (1.0 gram) coadministered to subjects with normal and abnormal renal function and with end-stage renal disease on hemodialysis." Antimicrob Agents Chemother, 33, p. 1470-6
  15. Rho JP, Jones A, Wood M, et al. (1989) "Single-dose pharmacokinetics of intravenous ampicillin plus sulbactam in healthy elderly and young adult subjects." J Antimicrob Chemother, 24, p. 573-80
  16. "Product Information. Polycillin-PRB (ampicillin-probenecid)." Apothecon Inc
  17. (2002) "Product Information. Spectrobid (bacampicillin)." Roerig Division
  18. (2002) "Product Information. Geocillin (carbenicillin)." Roerig Division
  19. (2002) "Product Information. Mezlin (mezlocillin)." Bayer
  20. (2001) "Product Information. Pfizerpen (penicillin)." Roerig Division
  21. (2001) "Product Information. Pipracil (piperacillin)." Lederle Laboratories
  22. (2001) "Product Information. Ticar (ticarcillin)." SmithKline Beecham
View all 22 references

Piperacillin (applies to Zosyn) cystic fibrosis

Moderate Potential Hazard, Moderate plausibility.

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


  1. (2001) "Product Information. Zosyn (piperacillin-tazobactam)." Lederle Laboratories

Piperacillin (applies to Zosyn) seizures

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Renal Dysfunction

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). Therapy with piperacillin should be administered cautiously in patients with preexisting neuromuscular excitability or seizure disorders.


  1. (2001) "Product Information. Zosyn (piperacillin-tazobactam)." Lederle Laboratories

Piperacillin (applies to Zosyn) sodium/potassium

Moderate Potential Hazard, Low plausibility. Applicable conditions: Hypokalemia, Congestive Heart Failure, Fluid Retention, Hypertension, Hypernatremia

Parenteral piperacillin sodium contains approximately 43 mg (1.85 mEq) of sodium per each gram of piperacillin activity. The combination, piperacillin-tazobactam, contains approximately 54 mg (2.35 mEq) of sodium per gram of piperacillin, or 108 mg (4.7 mEq) per 2.25 gram of total drug. The sodium content should be considered in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention. In addition, hypokalemia has been reported rarely during therapy with piperacillin and other extended-spectrum penicillin antibiotics, which may be particularly important to bear in mind when treating patients with low potassium reserves or fluid and electrolyte imbalance. Clinical monitoring of electrolytes is recommended if these agents are used for prolonged periods.


  1. Nanji AA, Lindsay J (1982) "Ticarcillin associated hypokalemia." Clin Biochem, 15, p. 118-9
  2. (2001) "Product Information. Ticar (ticarcillin)." SmithKline Beecham
  3. (2001) "Product Information. Zosyn (piperacillin-tazobactam)." Lederle Laboratories

Zosyn drug interactions

There are 54 drug interactions with Zosyn (piperacillin / tazobactam).

Zosyn alcohol/food interactions

There is 1 alcohol/food interaction with Zosyn (piperacillin / tazobactam).

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.