Piperacillin & Tazobactam

A Medico-Marketing Presentation on Piperacillin & Tazobactam

1. Piperacillin &
Tazobactam

2. COMPLICATION OF NOSOCOMIAL
INFECTIONS
Nosocomial infections are
estimated to double the
mortality and morbidity risks
of any admitted patient

3. NOSOCOMIAL TROIKA
Staphylococcus aureus
Escherichia coli
Pseudomonas aeruginosa

4. What is Resistance?
◦Drug Resistancerefers to unresponsiveness of a
microorganism to an antimicrobial agent.
◦Drug resistance is of two types:
Natural resistance
Acquired resistance

5. Natural resistance
◦Some microbes have always been resistant to certain antimicrobial
agents.
◦They lack the metabolic process or the target site that is affected by the
particular drug.
Gram negative bacilli are normally unaffected by penicillin G
M. tuberculosisis insensitive to tetracyclines.
◦This type of resistance does not pose significant clinical problem.
Acquired resistance:
◦It is the development of resistance by an organism (which was sensitive
before) due to the use of an antimicrobial agent over a period of time.
◦This can happen with any microbe and is a major clinical problem.
However, development of resistance is dependent on the
microorganism as well as the drug.

6. Porins
Altered penicillin binding proteins
-lactamases

7. CHALLENGES OF -LACTAMASES
1940 :Introduction of penicillins
1940 :First description of -lactamases published
1944 :Strains of staphylococcus aureus producing
-lactamase
1960s :Clinical use of expanded spectrum penicillins
-such as ampicillin and carbenicillin
1970s :plasmid mediated -lactamases assumed prominence in
enterobacteriaceae and gram-negative bacteria
1980-90:Development of broad-spectrum cephalosporins, cephamycins,
monobactams and carbapenems
1990 :Increased resistance among gram-negative bacteria with
inducible chromosomally-mediated lactamases
JAC (1993); suppl A: 1-8

8. EGASTSTUDY
Organism EGAST results
Proteus vulgaris 74%
S.epidermidis 73%
Klebsiella spp. 68%
Staphylococcus aureus 64%
Escherischia coli 64%
Citrobacter spp. 63%
Pseudomonas aeruginosa 59%
Enterobacter spp. 58% -70%
Proteus mirabilis 46%
Acinetobacter species 36%
Enterococcus faecalis 17%
Haemophilus influenzae 17%
International Journal of Antimicrobial Agents Volume 20, Issue 6, December 2002, Pages 426-431
Listing of organisms tested and their resistance features (212 isolates from India, 2000-2001)
No. of isolates=61%
Expert Group on Antibiotic Susceptibility Tests

9. FAILURE OF ANTIBIOTICS DUE TO
BETA-LACTAMASE
Current Rate of
Resistance
% increase in Resistance
(99 v/s 94-98)
Vancomycin/enterococci 25.9% 47%
Methicillin/S. aureus 54.5% 43%
Methicillin/Coagulase-negative
staphylococci
86.7% 2%
3
rd
generation Cephalosporin
Enterobacter spp
36.4% 3%
Imipenem/P. aeruginosa 18.5% 35%
Quinolone/P. aeruginosa 23.0% 49%
Am J Infect Control 1999;27:520-32

10. SOLUTION
-lactamase Inhibitors
Tazobactam –irreversible
‘suicide inhibitor’
Clavulanic acid
Sulbactam

11. INHIBITORY ACTIVITY OF -LACTAMASE INHIBITORS AGAINST
-LACTAMASES
Inhibitory Activity
c
Enzyme class
a
Organism
b
Tazobactam Clavulanic acidSulbactam
1a Enterobacter cloacae + 0 +
1b Escherichia coli + 0 0
1c Bacteroides fragilis
Proteus vulgaris + + + + + + +/+ + +
1d Pseudomonas + 0 +
aeruginosa
II Proteus mirabilis + + + + + + + +
III E.coli TEM-1 + + + + + 0
E.coli SHV-1 + + + +++ 0
IV Klebsiella pneumoniae + + + + + + +
V E.coli OXA-1 + + +
E.coli PSE-1 +++ +++ ++
Staphylococcus aureus ++ ++ +
a
Based on Richmond and Sykes Classification
b
Enzymes stated were those produced by organism studied
c
+ + + = IC50 < 0.05 mg/L + + = IC50 > 0.05 -< 0.5 mg/L + = IC50 > 0.5 -< 5 mg/L;
where IC50 is [the drug concentration required to reduce the initial rate of hydrolysis by 50%].

12. The extended spectrum
antipseudomonal penicillin:
Piperacillin
And Tazobactam–the potent
-lactamase inhibitor
INTRODUCING…

13. MODE OF ACTION
Piperacillin inhibits cell wall synthesis by binding to
penicillin-binding proteins in the cytoplasmic membrane of
bacteria.Porin
Penicillin Binding
Proteins (PBP)
cell wall synthesis P o rin
B e ta -la cta m
Ly s is
P e n ic illin B in d in g
P ro te in s (P B P )
c e ll w a ll sy n th e s is

14. PHARMACOKINETICS
Administered parenterally (IM, IV)
Piperacillin: Tazobactam available in 8: 1 ratio
Rapid Distribution within 30 minutes
Good concentration in the lungs, G.I. tissue and
muscle/fat tissues
Minimally protein bound
Excretion via kidneys
Drugs 1999;57:805-843

15. SERIOUS NOSOCOMIAL LRTIs
a. Serious Nosocomial LRTIs
Piperacillin-tazobactam plus tobramycin v/s ceftazidime plus tobramycin
(n = 155) (n = 145)In serious nosocomial LRTIs- Superior to Ceftazidime + Tobramycin
74%
78%
100%
69%
67%
50%
38%
50%
33%
30%
0% 20%40%60%80%100%120%
Clinical efficacy
Bacterial
eradication
H.influenzae
S.aureus
P.aeruginosa
Cefazidime + tobramycin
Piperacillin + tazobcatam
Conclusion: Piperacillin-Tazobactam proved to be superior to ceftazidime
plus tobramycin in the treatment of serious nosocomial LRTIs
% Efficacy
J. Antimicrob Chemotherapy 1999; 43, 389-397

16. INTRA-ABDOMINAL INFECTIONS
Piperacillin-tazobactam (4.5 g 8 hourly) v/s. Imipenem-cilastatin
(500 mg /500 mg 8 hourly)
n = 134
Conclusion:Data showed statistically significant difference in favour of piperacillin/tazobactam
Drugs 1999; 57(5): 83691 92
2 2
69
75.5
16
2
0
20
40
60
80
100
Clinica l cure rate
Ba cte riological eradicatin
Re laps e Rate
Treatment Fa ilures
Piperacillin-TazobactamImipenem/Cilastatin
% Efficacy

17. FEVER IN NEUTROPENIC CANCER
PATIENTS
Piperacillin-tazobactam (4.5 g 8 hourly) v/s. ceftazidime (2 g 8 hourly)
plus amikacin (15 mg/kg IV/day)
Fever in Neutropenic Cancer Patients Support Care. Cancer 1998; 6: 402-409
n=83 patients
Conclusion: Piperacillin-tazobactam is a safe and effective monotherapy
81%
83%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Success rate
PIP/TAZ CEFTAZIDIME

18. BACTEREMIA
Data were retrospectively pooled from nine studies
The underlying infections most often associated with
bacteraemia in these studies were:
Urinary tract infection (28%)
Neutropenia (27%) and
Intra-abdominal sepsis (15%)
n = 142 had microbiologically documented bacteraemia
No. of pathogens = 162
No. of pathogens eradicated = 151
Bacteriological cure = 93%
J Antimicrob Chemo 1993; 31(suppl A): 97-104

19. OTHER INFECTIONS
Piperacillin-tazobactam achieved a high clinical efficacy and bacteriological eradication
rate in various other infections as given below:
Drugs 1999; 57(5): 82791%
71%
82%
95%
96%
78%
86%
92.9%
0 20 40 60 80 100 120
Bone & Joint
Infections
Gynaecological
Infections
Urinary Tract
Infections
Skin and Soft Tissue
Infection
Bacterial EfficacyClinical Efficacy
% Efficacy

20. SAFETY AND TOLERABILITY 0
5
10
15
20
25
30
P ip -Ta zP ip -Ta z +a m in o g lyc o sid eIP M / C
O th e r sk in
e ve n t s
R a shO th e r G I
e ve n t s
N a u s e aD ia rrh o e a
I
n
c
i
d
e
n
c
e

(
%

o
f

p
a
t
i
e
n
t
s
)

21. HIGHLIGHTS
Piperacillin–Tazobactam is an injectable antibacterial
Piperacillin sodium is a extended spectrum penicillin
belonging to ureidopenicillin class
Tazobactam sodium is a penicillanic acid sulfone and a potent
-lactamase inhibitor (suicide inhibitor)
Distribution of both piperacillin-tazobactam is rapid and
occurs within 30 minutes of infusion.
Good penetration in many tissues, with concentrations which
exceed the MIC90s of most bacterial species

22. HIGHLIGHTS
Remarkable success in the treatment of various
polymicrobial infections like
Lower respiratory tract infection
Intra-abdominal infections
Complicated urinary tract
Serious skin and soft tissue infections
Febrile Neutropenia
Good safety profile
Low sodium content therefore can be safely used in
patients on salt restricted diets