Piperacillin sodium microbiology

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Piperacillin sodium
PIPRACIL® FDA Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Overdosage
Dosage and Administration
How Supplied

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamed Moubarak, M.D. [2]

Microbiology

Piperacillin is an antibiotic which exerts its bactericidal activity by inhibiting both septum and cell wall synthesis. It is active against a variety of gram-positive and gram-negative aerobic and anaerobic bacteria. Piperacillin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

  • 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-β-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

The following in vitro data are available, but their clinical significance is unknown.

At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for piperacillin. However, the safety and effectiveness of piperacillin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

  • Aerobic gram-positive microorganisms

Streptococcus agalactiae

Streptococcus bovis

Viridans group streptococci

  • Aerobic gram-negative microorganisms

Burkholderia cepacia

Citrobacter diversus

Citrobacter freundii

Pseudomonas fluorescens

Stenotrophomonas maltophilia

Yersinia enterocolitica

  • Anaerobic gram-positive microorganisms

Actinomyces species

Eubacterium species

  • Anaerobic gram-negative microorganisms

Fusobacterium necrophorum

Fusobacterium nucleatum

Porphyromonas asaccharolytica

Prevotella melaninogenica Veillonella species

Susceptibility Testing Methods

  • Dilution Techniques:

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1,2 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of piperacillin powder. The MIC values should be interpreted according to the following criteria:

For testingEnterobacteriaceae and Acinetobacter species:

Haemophilus species are considered susceptible if the MIC of piperacillin is≤ to 1 μg/mL.*

  • Dilution methods such as those described in the International Collaborative Study (Acta Pathol Microbiol Scand [B] 1971; suppl 217) have been used to determine susceptibility of organisms to piperacillin.

Dilution (MICs) susceptibility test methods and interpretative criteria for assessing the susceptibility of Neisseria gonorrhoeae to piperacillin have not been established. However,β‑lactamase testing will detect one form of penicillin resistance in Neisseria gonorrhoeae and is recommended.1,2

Dilution (MICs) susceptibility test methods and interpretative criteria for assessing the susceptibility of Streptococcus pneumoniae and Streptococcus pyogenes to piperacillin have not been established.1,2

A report of“Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

  • Quality Control:

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard piperacillin powder should provide the following MIC values:

  • Diffusion Techniques:

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 100μg of piperacillin to test the susceptibility of microorganisms to piperacillin.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 100 μg piperacillin disk should be interpreted according to the following criteria:

For testing Enterobacteriaceae and Acinetobacter species:

Haemophilus species which give zones of ≥ 29 mm are susceptible; resistant strains give zones of ≤ 28 mm. The above interpretive criteria are based on the use of the standardized procedure. Antibiotic susceptibility testing requires carefully prescribed procedures. Susceptibility tests are biased to a considerable degree when different methods are used.

NCCLS Approved Standard; M2-A2 (Formerly ASM-2) Performance Standards for Antimicrobic Disk Susceptibility Tests, Second Edition, available from the National Committee of Clinical Laboratory Standards.

Disk diffusion (zone diameters) susceptibility test methods and interpretative criteria for assessing the susceptibility of Neisseria gonorrhoeae to piperacillin have not been established. However, β-lactamase testing to penicillin is recommended. It will detect one form of penicillin resistance, chromosomally mediated resistance, in Neisseria gonorrhoeae. In addition, gonococci with 10-unit penicillin disk zone diameters of ≤ 19 mm are likely to be β-lactamase producing strains (plasmid-mediated penicillin resistance).2,3

Disk diffusion (zone diameters) susceptibility test methods and interpretative criteria for assessing the susceptibility of Streptococcus pneumoniae and Streptococcus pyogenes to piperacillin have not been established.2,3

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for piperacillin.

  • Quality Control:

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 100-μg piperacillin disk should provide the following zone diameters in these laboratory test quality control strains:

Escherichia coli ATCC 25922 Zone Diameter (mm):24-30

Pseudomonas aeruginosa ATCC 27853 Zone Diameter (mm):25-33

  • Anaerobic Techniques:

For anaerobic bacteria, the susceptibility to piperacillin as MICs can be determined by standardized test methods.4 The MIC values obtained should be interpreted according to the following criteria:

≤ 32μg/mL Susceptible (S)
64μg/mL Intermediate (I)
≥ 128μg/mL Resistant (R)

Interpretation is identical to that stated above for results using dilution techniques.

As with other susceptibility techniques, the use of laboratory control microorganisms is required to control the technical aspects of the laboratory standardized procedures. Standardized piperacillin powder should provide the following MIC values:

Bacteroides fragilisc: ATCC 25285 2-8μg/mL
Bacteroides thetaiotaomicrond : ATCC 29741 8-32μg/mL[1]

References

  1. "PIPRACIL (PIPERACILLIN SODIUM) INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [WYETH PHARMACEUTICALS, INC.]". Text " accessdate" ignored (help)

Adapted from the FDA Package Insert.