Piperacin

	Zambia HIV National Guidelines
	Introduction HIV Counseling and Testing Sexually Transmitted Infections (STIs) General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents Initial Regimen for ARV Therapy Adherence Baseline evaluation and Monitoring Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance ARV Therapy for Individuals with Tuberculosis Co-Infection Adverse Effects and Toxicity Immune Reconstitution Inflammatory Syndrome (IRIS) Changing or Stopping ART Treatment Failure Stopping ARV Therapy Post Exposure Prophylaxis Cotrimoxazole Prophylaxis WHO Staging in Adults and Adolescents Nutrition Care and Support Palliative Care in HIV and AIDS
	Guide Editors
	Editor In Chief Joel E. Gallant, MD, MPH Pharmacology Editor Paul Pham, PharmD, BCPS Zambia Guideline Team Peter Mwaba MMed PhD FRCP Alywn Mwinga MMed Isaac Zulu MMed MPH Velepie Mtonga MMed Albert Mwango MBChB Jabbin Mulwanda MMed FCS

Drugs>Antimicrobial Agents>

Piperacillin

Paul A. Pham Pharm.D. and John G. Bartlett M.D.
08-05-2009

Zambia Specific Information

Available formulation in Zambia: IV: 2 g, 4 g/vial
Pseudomonas pneumonia: piperacillin 300mg/kg/d divided q4h (3 gm IV q4h) plus gentamicin.

Zambia Information Author: Paul A. Pham Pharm.D.

INDICATIONS

FDA

Bone and joint infections
Gonococcal infections
Gynecologic infections
Intra-abdominal infections
Lower respiratory tract infections
Septicemia
Skin and skin structure infections
Surgical prophylaxis (intra-abdominal procedure, vaginal hysterectomy, abdominal hysterectomy, c-section)
Urinary tract infections

FORMS

brand name	generic	Mfg	brand forms	cost*
Piperacillin	Piperacillin	~Various generic manufacturers	IV vial 3g	$13.05
			IV vial 4g	$17.40
			IV vial 40g	$161.25
			IV vial 2g	$8.70

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

Moderate to severe infections: 3gm IV q4-6h (up to 24 gm a day).
Pneumonia and pseudomonal infections: 3gm IV q4h or 4gm IV q6h.

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

GFR >40 mL/min: 3 gm q6h. Use 3 gm q4h or 4 gm q6h for severe infections or Pseudomonas.

DOSING FOR GLOMERULAR FILTRATION OF 10-50

GFR 20-40 mL/min: 2 gm q6h. For severe infection or Pseudomonas 4 gm q8h.

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

GFR <20 mL/min: 2 gm q8h or 3 gm q12h. Use 4 gm q12h for severe infections or Pseudomonas.

DOSING IN HEMODIALYSIS

2 gm q8h plus 1 gm post-dialysis. For severe infections 3 gm q8h plus 1 gm post dialysis.

DOSING IN PERITONEAL DIALYSIS

2 gm q8h. For severe infection 3 gm q8h.

DOSING IN HEMOFILTRATION

CVVH: 2 gm q6h. CVVHD: 2-3 gm q6h;severe infections: 3 gm IV q6-8h.

ADVERSE DRUG REACTIONS

GENERAL

Generally well tolerated

OCCASIONAL

GI intolerance
Phlebitis at infusion sites
Jarisch-Herxheimer reaction (with syphilis or other spirochetal infections)
C. difficile colitis
LFTs elevations with rare cases of clinical hepatitis
Hypersensitivity reactions
Rash

RARE

Drug fever
Coombs' test positive w/ hemolytic anemia
Interstitial nephritis
Neutropenia and thrombocytopenia
Abnormal platelet aggregation with bleeding diathesis
CNS: seizures and twitching ( with high doses in patients with renal failure)
Hepatitis
Anaphylaxis

DRUG INTERACTIONS

Methotrexate: serum concentrations may be increased. Monitor with methotrexate-induced toxicity.
Probenecid: may prolong piperacillin half-life. May be result in significant accumulation in renal failure.
Tetracyclines: in vitro antagonism when co-administered. Bactericidal effect of penicillins may be diminished in vivo. Management recommendation: avoid concurrent administration. In two studies involving a total of 79 patients with pneumococcal meningitis treated with either penicillin plus tetracyclines or penicillin monotherapy resulted in a higher mortality rate (79-85%) in the combination therapy compared to penicillinmonotherapy (30-33%) [Arch Intern Med 1951:88:489, Ann Intern Med 1961; 55:545]. However there was not a difference in mortality between penicillin monotherapy and penicillin plus tetracycline in the treatment of pneumococcal pneumonia [Arch Intern Med 1953; 91:197].

SPECTRUM

Detailed Spectrum of Activity

RESISTANCE

MIC breakpoint for Enterobacteriaceae and Gram-negative non-lactose fermenters is 16 mcg/mL (except P. aeruginosa).
Current MIC breakpoint for P. aeruginosa is 64 mcg/mL (in part due to historical use of piperacillin always combined with an aminoglycoside), but pharmacokinetics of piperacillin are suboptimal for strains with MIC of 32 and 64 mcg/mL. Avoid piperacillin in these cases or use in combination with an aminoglycoside.

PHARMACOLOGY

Pharmacology

COMMENTS

Parenteral anti-pseudomonal penicillin with superior enterococcal coverage compared to ticarcillin. Due to the high prevalence of plasmid-mediated beta-lactamases produced by gram-negative bacteria, piperacillin without tazobactam is not recommended empirically for nosocomial infections. If sensitive to piperacillin, may be preferred over piperacillin-tazobactamfor P. aeruginosa as the tazobactam does not add activity against pseudomonas.

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