Piperacillin/Tazobactam: Difference between revisions
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==General== | ==General== | ||
*Type: Anti-Pseudomonal [[Penicillin]] | *Type: Anti-Pseudomonal [[Penicillin]] | ||
*Dosage Forms: | *Dosage Forms: 2.25gm vial, 3.375gm vial, 4.5gm vial, 40.5gm bulk bottle (Powder for reconstitution) | ||
*Common Trade Names: Zosyn | *Common Trade Names: Zosyn | ||
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*Alt: 4.5 g q6-8 hours | *Alt: 4.5 g q6-8 hours | ||
*Max: 18 g/day | *Max: 18 g/day | ||
===Extended Interval Dosing=== | |||
*3.375 g IV infused over 4 hours q8 hours | |||
**Off-label: may reduce costs without sacrificing efficacy<ref>Shea KM, Cheatham SC, Smith DW, Wack MF, Sowinski KM, Kays MB. Comparative pharmacodynamics of intermittent and prolonged infusions of [[piperacillin/tazobactam]]using Monte Carlo simulations and steady-state pharmacokinetic data from hospitalized patients. Ann Pharmacother. 2009;43(11):1747-54.</ref><ref>Kaufman SE, Donnell RW, Hickey WS. Rationale and evidence for extended infusion of piperacillin-tazobactam. [http://www.ncbi.nlm.nih.gov/pubmed/21817083 Am J Health Syst Pharm. 2011 Aug 15;68(16):1521-6.]</ref> | |||
===[[Diverticulitis]]=== | ===[[Diverticulitis]]=== | ||
* | *{{Piperacillin/Tazobactam Diverticulitis}} | ||
===[[Pneumonia]]=== | ===[[Pneumonia]]=== | ||
Line 18: | Line 22: | ||
**Only for P. aeruginosa caused or from aspiration<ref>Mandell, 2007</ref> | **Only for P. aeruginosa caused or from aspiration<ref>Mandell, 2007</ref> | ||
*Nosocomial | *Nosocomial | ||
**4.5 g IV q6 hours x 7-14 days | **4.5 g IV q6 hours or 3.375 g IV q4 hours x 7-14 days | ||
**+ aminoglycoside or antipseudomonal fluoroquinolone | **+ aminoglycoside or antipseudomonal fluoroquinolone | ||
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===General=== | ===General=== | ||
*'''<2 months''' | *'''<2 months''' | ||
** | **100mg piperacillin/kg/dose IV q6 hours | ||
*'''2-9 months''' | *'''2-9 months''' | ||
** | **80mg piperacillin/kg/dose IV q8 hours | ||
*'''>9 months''' | *'''>9 months''' | ||
** | **100mg piperacillin/kg/dose q8 hours | ||
*Max: 16 g/day | *Max: 16 g/day | ||
===Appendicitis and/or Peritonitis=== | ===[[Appendicitis]] and/or [[Peritonitis]]=== | ||
*2-9 months | *2-9 months | ||
** | **80mg piperacillin/kg/dose IV q8 hours | ||
*>9 months | *>9 months | ||
**≤40 kg: | **≤40 kg: 100mg piperacillin/kg/dose IV q8 hours | ||
**>40 kg: 3.375g ( | **>40 kg: 3.375g (3000mg piperacillin) IV q6 hours | ||
*Max: 16 g/day | *Max: 16 g/day | ||
===Cystic Fibrosis, Pseudomonal Infection=== | ===Cystic Fibrosis, Pseudomonal Infection=== | ||
*240- | *240-400mg piperacillin/kg/day IV divided q8 hours; | ||
**Consider higher dose: 450- | **Consider higher dose: 450-600mg/kg/day IV divided q4-6 hours<ref>Zobell JT, Waters CD, Young DC, et al, "Optimization of Anti-Pseudomonal Antibiotics for Cystic Fibrosis Pulmonary Exacerbations: II. Cephalosporins and Penicillins," Pediatr Pulmonol, 2013, 48(2):107-22. PubMed 22949297</ref> | ||
==Special Populations== | ==Special Populations== | ||
*Pregnancy: | *[[Drug pregnancy categories|Pregnancy risk]]: | ||
*Lactation: | *Lactation: | ||
*Renal Dosing | *Renal Dosing | ||
**Adult | **Adult - all indications<ref>GlobalRPH. Piperacillin/Tazobactam - Zosyn® - Renal Dosing. http://www.globalrph.com/piperacillin-tazobactam_renal.htm</ref><ref>Epocrates. Zosyn - Entire Monograph. https://online.epocrates.com/u/10a1657/Zosyn</ref> | ||
** | ***CrCl 20-40: 2.25 g q6h (3.375 g q6h if HCAP) | ||
* | ***CrCl < 20: 2.25 g q8h (2.25 g q6h if HCAP) | ||
** | ***HD: 2.25 g q12h (2.25 g q8h if HCAP), both PLUS 0.75 g supplement after each dialysis | ||
***PD: 2.25 g q12h (2.25 g q8h if HCAP) | |||
**Pediatric | **Pediatric | ||
*Hepatic Dosing - no change | |||
==Contraindications== | ==Contraindications== | ||
*Allergy to class/drug | *Allergy to class/drug | ||
*Caution | |||
**Non-anaphylactic hypersensitivity to beta-lactams | |||
**Asthma, cystic fibrosis | |||
**Recent antibiotic-associated colitis | |||
**Seizure disorder | |||
**Renal impairement | |||
**Sodium restriction | |||
**Hypokalemia | |||
**Bleeding risk | |||
==Adverse Reactions== | ==Adverse Reactions== | ||
===Serious=== | ===Serious=== | ||
*[[Anaphylaxis]] | |||
*Serum sickness-like reaction | |||
*[[DRESS syndrome]] | |||
*Acute generalized exanthematous pustulosis | |||
*[[Erythema multiforme]], [[SJS]], [[TEN]] | |||
*Interstitial nephritis | |||
*Superinfection | |||
*C. difficile associated [[diarrhea]] | |||
*[[Hemolytic anemia]], [[leukopenia]], [[neutropenia]], [[pancytopenia]], agranulocytosis, [[thrombocytopenia]] | |||
*Bleeding | |||
*[[Hypokalemia]] | |||
*[[Seizure]] | |||
===Common=== | ===Common=== | ||
*[[Diarrhea]], [[constipation]], [[nausea/vomiting]], dyspepsia | |||
*[[Headache]] | |||
*Insomnia | |||
*[[Rash]], [[pruritus]] | |||
*[[Fever]] | |||
*Agitation | |||
*Electrolyte abnormality | |||
*LFT elevation | |||
==Pharmacology== | ==Pharmacology== | ||
*Half-life: | *Half-life: | ||
**Pipercillin: 30-90 min | |||
**Tazobactam: 0.7-1.2h | |||
*Metabolism: | *Metabolism: | ||
**Pipercillin: Liver minimally | |||
**Tazobactam: Liver | |||
*Excretion: | *Excretion: | ||
**Pipercillin: Urine 68% | |||
**Tazobactam: Urine primarily | |||
*Mechanism of Action: | *Mechanism of Action: | ||
**Pipercillin: Inhibits cell wall mucopeptide synthesis | |||
**Tazobactam: Inhibits beta-lactamases | |||
==[[Antibiotic Sensitivities]]<ref>Sanford Guide to Antimicrobial Therapy 2014</ref>== | |||
{| class="wikitable" | |||
| align="center" style="background:#f0f0f0;"|'''Group''' | |||
| align="center" style="background:#f0f0f0;"|'''Organism''' | |||
| align="center" style="background:#f0f0f0;"|'''Sensitivity''' | |||
|- | |||
| Gram Positive||[[Strep. Group A, B, C, G]]||'''S''' | |||
|- | |||
| ||[[Strep. Pneumoniae]]||'''S''' | |||
|- | |||
| ||[[Viridans strep]]||I | |||
|- | |||
| ||Strep. anginosus gp||'''S''' | |||
|- | |||
| ||[[Enterococcus faecalis]]||'''S''' | |||
|- | |||
| ||[[Enterococcus faecium]]||I | |||
|- | |||
| ||[[MSSA]]||'''S''' | |||
|- | |||
| ||[[MRSA]]||R | |||
|- | |||
| ||[[CA-MRSA]]||R | |||
|- | |||
| ||[[Staph. Epidermidis]]||'''S''' | |||
|- | |||
| ||[[C. jeikeium]]||X1 | |||
|- | |||
| ||[[L. monocytogenes]]||X2 | |||
|- | |||
| Gram Negatives||[[N. gonorrhoeae]]||X2 | |||
|- | |||
| ||[[N. meningitidis]]||'''S''' | |||
|- | |||
| ||[[Moraxella catarrhalis]]||'''S''' | |||
|- | |||
| ||[[H. influenzae]]||'''S''' | |||
|- | |||
| ||[[E. coli]]||'''S''' | |||
|- | |||
| ||[[Klebsiella]] sp||'''S''' | |||
|- | |||
| ||E. coli/Klebsiella ESBL+||R | |||
|- | |||
| ||E coli/Klebsiella KPC+||R | |||
|- | |||
| ||[[Enterobacter]] sp, AmpC neg||'''S''' | |||
|- | |||
| ||[[Enterobacter]] sp, AmpC pos||'''S''' | |||
|- | |||
| ||[[Serratia]] sp||'''S''' | |||
|- | |||
| ||Serratia marcescens||X1 | |||
|- | |||
| ||[[Salmonella]] sp||'''S''' | |||
|- | |||
| ||[[Shigella]] sp||'''S''' | |||
|- | |||
| ||[[Proteus mirabilis]]||'''S''' | |||
|- | |||
| ||[[Proteus vulgaris]]||'''S''' | |||
|- | |||
| ||[[Providencia sp.]]||'''S''' | |||
|- | |||
| ||[[Morganella sp.]]||'''S''' | |||
|- | |||
| ||[[Citrobacter freundii]]||'''S''' | |||
|- | |||
| ||[[Citrobacter diversus]]||'''S''' | |||
|- | |||
| ||[[Citrobacter sp.]]||'''S''' | |||
|- | |||
| ||[[Aeromonas sp]]||'''S''' | |||
|- | |||
| ||[[Acinetobacter sp.]]||I | |||
|- | |||
| ||[[Pseudomonas aeruginosa]]||'''S''' | |||
|- | |||
| ||[[Burkholderia cepacia]]||X1 | |||
|- | |||
| ||[[Stenotrophomonas maltophilia]]||I | |||
|- | |||
| ||[[Yersinia enterocolitica]]||X1 | |||
|- | |||
| ||[[Francisella tularensis]]||X1 | |||
|- | |||
| ||[[Brucella sp.]]||X1 | |||
|- | |||
| ||[[Legionella sp.]]||R | |||
|- | |||
| ||[[Pasteurella multocida]]||X1 | |||
|- | |||
| ||[[Haemophilus ducreyi]]||X1 | |||
|- | |||
| ||[[Vibrio vulnificus]]||X1 | |||
|- | |||
| Misc||[[Chlamydophila sp]]||R | |||
|- | |||
| ||[[Mycoplasm pneumoniae]]||R | |||
|- | |||
| ||[[Rickettsia sp]]||X1 | |||
|- | |||
| ||[[Mycobacterium avium]]||X1 | |||
|- | |||
| Anaerobes||[[Actinomyces]]||X1 | |||
|- | |||
| ||[[Bacteroides fragilis]]||'''S''' | |||
|- | |||
| ||[[Prevotella melaninogenica]]||'''S''' | |||
|- | |||
| ||[[Clostridium difficile]]||X1 | |||
|- | |||
| ||[[Clostridium (not difficile)]]||'''S''' | |||
|- | |||
| ||[[Fusobacterium necrophorum]]||'''S''' | |||
|- | |||
| ||[[Peptostreptococcus sp.]]||'''S''' | |||
|} | |||
===Key=== | |||
{{Template:Antibacterial Spectra Key}} | |||
==See Also== | ==See Also== | ||
*[[Antibiotics (Main)]] | *[[Antibiotics (Main)]] | ||
==References== | |||
<references/> | <references/> | ||
[[Category: | [[Category:Pharmacology]] |
Revision as of 16:46, 19 November 2017
General
- Type: Anti-Pseudomonal Penicillin
- Dosage Forms: 2.25gm vial, 3.375gm vial, 4.5gm vial, 40.5gm bulk bottle (Powder for reconstitution)
- Common Trade Names: Zosyn
Adult Dosing
General
- 3.375 g IV q6 hours
- Alt: 4.5 g q6-8 hours
- Max: 18 g/day
Extended Interval Dosing
- 3.375 g IV infused over 4 hours q8 hours
Diverticulitis
- 3.375 g IV q6 hours x 7-10 days
Pneumonia
- CAP
- 3.375 g IV q6 hours x 7-10 days
- Only for P. aeruginosa caused or from aspiration[3]
- Nosocomial
- 4.5 g IV q6 hours or 3.375 g IV q4 hours x 7-14 days
- + aminoglycoside or antipseudomonal fluoroquinolone
Pediatric Dosing[4]
A Piperacillin/Taxobactam 3.375g vial contains 3g piperacillin and 0.375g tazobactam (8:1 ratio)
General
- <2 months
- 100mg piperacillin/kg/dose IV q6 hours
- 2-9 months
- 80mg piperacillin/kg/dose IV q8 hours
- >9 months
- 100mg piperacillin/kg/dose q8 hours
- Max: 16 g/day
Appendicitis and/or Peritonitis
- 2-9 months
- 80mg piperacillin/kg/dose IV q8 hours
- >9 months
- ≤40 kg: 100mg piperacillin/kg/dose IV q8 hours
- >40 kg: 3.375g (3000mg piperacillin) IV q6 hours
- Max: 16 g/day
Cystic Fibrosis, Pseudomonal Infection
- 240-400mg piperacillin/kg/day IV divided q8 hours;
- Consider higher dose: 450-600mg/kg/day IV divided q4-6 hours[5]
Special Populations
- Pregnancy risk:
- Lactation:
- Renal Dosing
- Hepatic Dosing - no change
Contraindications
- Allergy to class/drug
- Caution
- Non-anaphylactic hypersensitivity to beta-lactams
- Asthma, cystic fibrosis
- Recent antibiotic-associated colitis
- Seizure disorder
- Renal impairement
- Sodium restriction
- Hypokalemia
- Bleeding risk
Adverse Reactions
Serious
- Anaphylaxis
- Serum sickness-like reaction
- DRESS syndrome
- Acute generalized exanthematous pustulosis
- Erythema multiforme, SJS, TEN
- Interstitial nephritis
- Superinfection
- C. difficile associated diarrhea
- Hemolytic anemia, leukopenia, neutropenia, pancytopenia, agranulocytosis, thrombocytopenia
- Bleeding
- Hypokalemia
- Seizure
Common
- Diarrhea, constipation, nausea/vomiting, dyspepsia
- Headache
- Insomnia
- Rash, pruritus
- Fever
- Agitation
- Electrolyte abnormality
- LFT elevation
Pharmacology
- Half-life:
- Pipercillin: 30-90 min
- Tazobactam: 0.7-1.2h
- Metabolism:
- Pipercillin: Liver minimally
- Tazobactam: Liver
- Excretion:
- Pipercillin: Urine 68%
- Tazobactam: Urine primarily
- Mechanism of Action:
- Pipercillin: Inhibits cell wall mucopeptide synthesis
- Tazobactam: Inhibits beta-lactamases
Antibiotic Sensitivities[8]
Key
- S susceptible/sensitive (usually)
- I intermediate (variably susceptible/resistant)
- R resistant (or not effective clinically)
- S+ synergistic with cell wall antibiotics
- U sensitive for UTI only (non systemic infection)
- X1 no data
- X2 active in vitro, but not used clinically
- X3 active in vitro, but not clinically effective for Group A strep pharyngitis or infections due to E. faecalis
- X4 active in vitro, but not clinically effective for strep pneumonia
See Also
References
- ↑ Shea KM, Cheatham SC, Smith DW, Wack MF, Sowinski KM, Kays MB. Comparative pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactamusing Monte Carlo simulations and steady-state pharmacokinetic data from hospitalized patients. Ann Pharmacother. 2009;43(11):1747-54.
- ↑ Kaufman SE, Donnell RW, Hickey WS. Rationale and evidence for extended infusion of piperacillin-tazobactam. Am J Health Syst Pharm. 2011 Aug 15;68(16):1521-6.
- ↑ Mandell, 2007
- ↑ Red Book, 2012
- ↑ Zobell JT, Waters CD, Young DC, et al, "Optimization of Anti-Pseudomonal Antibiotics for Cystic Fibrosis Pulmonary Exacerbations: II. Cephalosporins and Penicillins," Pediatr Pulmonol, 2013, 48(2):107-22. PubMed 22949297
- ↑ GlobalRPH. Piperacillin/Tazobactam - Zosyn® - Renal Dosing. http://www.globalrph.com/piperacillin-tazobactam_renal.htm
- ↑ Epocrates. Zosyn - Entire Monograph. https://online.epocrates.com/u/10a1657/Zosyn
- ↑ Sanford Guide to Antimicrobial Therapy 2014