3rd gen. injectable

1. http://www.liebertonline.com/doi/abs/10.1089/10962960152742196?cookieSet=1&journalCode=sur
Surgical Infections, Jun 2001, Vol. 2, No. supplement 1 : 23 -32
The Role of β-Lactam/β-Lactamase Inhibitor Combinations in Surgical
Infections
Iskender Sayek Hacettepe University School of Medicine, Ankara, TurkeyMany
surgical infections are characterized by synergistic polymicrobial mixed infection,
for which broad-spectrum antimicrobial therapy is usually administered on an
empiric basis. Until relatively recently, standard empiric therapeutic regimens
have involved the use of two or more antibiotics, such as aminoglycosides
and anti-anaerobic agents, to achieve adequate aerobic and anaerobic
coverage. There are often substantial drawbacks, however, such as drug-
induced toxicity and high costs of treatment. Evidence from a number of
clinical studies suggests that single-agent therapy with β-lactam/β-lactamase
inhibitor combinations is a suitable and cost-effective alternative to
multidrug regimens, as well as to monotherapy with cephalosporins or
carbapenems in the treatment of intra-abdominal, gynecologic, and diabetic
foot infections, and brain abscesses. These agents are also suitable for use in
perioperative prophylaxis and may offer benefits over other agents in terms of
reduced incidence of surgical wound infections and lower costs.

2. Disadvantages of standard empiric therapeutic regimens
use of two or more antibiotics,
such as aminoglycosides (e.g. Gentamicin, Amikacin) and anti-
anaerobic agents (Metronidazole),
• to achieve adequate aerobic and anaerobic coverage.
• Drug-induced toxicity and high costs of treatment.
Justification of single-agent therapy with β-lactam/β-lactamase
inhibitor combinations
• is a suitable and cost-effective alternative to multidrug regimens, as
well as to monotherapy with cephalosporins or carbapenems in the
treatment of
•intra-abdominal, gynecologic, and diabetic foot infections, and
brain abscesses.
•also suitable for use in perioperative prophylaxis
• reduced incidence of surgical wound infections and lower costs.
The Role of β-Lactam/β-Lactamase Inhibitor Combinations in Surgical Infections

3. http://jac.oxfordjournals.org/cgi/content/abstract/25/2/199
Journal of Antimicrobial Chemotherapy (1990) 25, 199-208
© 1990 The British Society for Antimicrobial Chemotherapy
research-article
Interactions of tazobactam and clavulanate with inducibly- and constitutively-expressed Class I ß-
lactamases
M. Akova, Youjun Yang and D. M. Livermore
*
Department of Medical Microbiology, The London Hospital
Medical College Turner Street, London E1 2AD, UK
Received 10 August 1989; accepted 14 September 1989
*
Corresponding author Clavulanate and tazobactam (YTR 830) were tested as inhibitors and
inducers of the AmpC-type Class I ß-lactamases of Pseudomonas aeruginosa, Enterobacter
cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii and the Ic ßlactamase of
Proteus vulgaris. Both clavulanate and tazobactam inhibited the Pr. vulgaris Class Ic ßlactamase
and potentiated ticarcillin and piperacillin against ß-lactamase derepressed variants of this species.
Tazobactam, but not clavulanate, also had some ability to inhibit the AmpC Class I enzymes
of M. morganii, C. freundii, Ps. aeruginosa, E. cloacae and S. marcescens. The piperacillin +
tazobactam combination, unlike ticarcillin + clavulanate, showed some degree of synergy against
most derepressed strains of these species. This behaviour partly depended upon the greater
inhibitory activity of tazobactam for the enzymes, but also on piperacillin being easier to
potentiate than ticarcillin. The synergy between piperacillin and tazobactam was greatest for M.
morganii and C. freundii, least for Ps. aeruginosa and E. cloacae. Unfortunately, it is in the last two
species that these enzymes pose the greatest resistance threat Tazobactam caused little or no
antagonism of piperacillin against ß-lactamase inducible species, whereas clavulanate
antagonized ticarcillin against ß-lactamase inducible strains of E. cloacae and M. morganii (not
other species). The antagonism of ticarcillin was attributable to ß-lactamase induction. The
lack of antagonism with the tazobactam + piperacillin combination was related to tazobactam
being a weaker inducer than clavulanate, not to piperacillin being less susceptible to antagonism

4. Interactions of tazobactam and clavulanate with
inducibly- and constitutively-expressed Class I ß-
lactamases
(piperacillin + tazobactam & ticarcillin + clavulanate )
Tazobactam, but not clavulanate, also had some ability to inhibit the AmpC
Class I enzymes of M. morganii, C. freundii, Ps. aeruginosa, E. cloacae and S.
marcescens.
The piperacillin + tazobactam combination, unlike ticarcillin + clavulanate, showed
some degree of synergy against most derepressed strains of these species.
This behaviour partly depended upon the greater inhibitory activity of
tazobactam for the enzymes.
Antagonism characteristics
The synergy between piperacillin and tazobactam was greatest for M. morganii and
C. freundii, least for Ps. aeruginosa and E. cloacae.
Unfortunately, it is in the last two species that these enzymes pose the greatest
resistance threat Tazobactam caused little or no antagonism of piperacillin
against ß-lactamase inducible species, whereas clavulanate antagonized ticarcillin
against ß-lactamase inducible strains of E. cloacae and M. morganii (not other
species).

5. http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=2302&XNSPRACHE_ID=2&XNKONGRESS_ID=11&XNMASKEN_ID=900
15th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)
02.04.2005 - 05.04.2005
In vitro activity of antimicrobial agents
Effect of beta-lactamase-inhibitor concentrations on in vitro test results with
piperacillin/tazobactam and piperacillin/sulbactam
H. Grimm, J. Wagner, A.C. Rodloff (Weingarten, Berlin, Leipzig, D)
Objectives: Recently, DIN 58940 was altered, now recommending to test the beta-lactamase
inhibiting effect of Sulbactam in presence of a constant concentration of 4 mg/L instead of previously
8 mg/L. The present study was performed to assess the effect of this change on the MIC
distributions of E. coli for Piperacillin/Sulbactam (P/S) as compared to Piperacillin/Tazobactam (P/T)
with Tazobactam tested at a concentration of 4 mg/L.
Methods: The in-vitro activity of Piperacillin without and with Tazobactam or Sulbactam, respectively,
against E. coli (n = 2856 in Leipzig, n = 420 in Berlin) was tested by means of microdilution MIC
determinations as recommended by DIN 58940 using a fixed concentration of 4 mg/L of Tazobactam
and 4 as well as 8 mg/L of Sulbactam.
Results: On the basis of MIC breakpoints according to DIN, the superiority of P/T over P/S is
maximal in Piperacillin-resistant E. coli and minimal in Piperacillin-intermediate E. coli. The
recently recommended reduction of the fixed Sulbactam concentration (from 8 to 4 mg/L) in
susceptibility tests leads to reduced susceptibility in Piperacillin-intermediate E. coli, too. The results
are as follows: (table)
Conclusion: The recently recommended 4 mg/L fixed concentration of Sulbactam in testing
procedures shows that the in-vitro activity of P/T exceed those of P/S not only in Piperacillin-resistant
but also in Piperacillin-intermediate E. coli. These results are credible because of the stronger
inhibition of TEM-1 lactamases by Tazobactam in comparison to Sulbactam.

6. Effect of beta-lactamase-inhibitor concentrations on in vitro test results with
piperacillin/tazobactam and piperacillin/sulbactam
test the beta-lactamase inhibiting effect of Sulbactam in presence of a
constant concentration of 4 mg/L instead of previously 8 mg/L.
the MIC distributions of E. coli for Piperacillin/Sulbactam (P/S) as compared
to Piperacillin/Tazobactam (P/T) with Tazobactam tested at a concentration
of 4 mg/L.
Results: On the basis of MIC breakpoints according to DIN, the
superiority of P/T over P/S is maximal in Piperacillin-resistant E. coli
and minimal in Piperacillin-intermediate E. coli.
Conclusion: It shows that the in-vitro activity of P/T exceed those of P/S
not only in Piperacillin-resistant but also in Piperacillin-intermediate E.
coli.
These results are credible because of the stronger inhibition of TEM-1
lactamases by Tazobactam in comparison to Sulbactam.