In vitro activity of penicillin G/sulbactam compared with penicillin and other antibiotics against common organisms causing ear, nose and throat (ENT) infections

S. Wenzler*, E. Schmidt-Eisenlohr and F. Daschner

Institute of Environmental Medicine and Hospital Epidemiology, Freiburg University Hospital, Hugstetter Str. 55, D-79106 Freiburg, Germany

Keywords: penicillin G/sulbactam, in vitro activity, ENT infections

Sir,

The ß-lactamase inhibitor sulbactam generally shows weak antibacterial activity. It possesses good activity against Acinetobacter and Neisseria spp., and is also effective against anaerobes, but only in doses much higher than those normally given to a patient. In combination with ß-lactam antibiotics, however, sulbactam develops a marked synergic effect, inhibiting certain ß-lactamases.

The antibiotic combination ampicillin/sulbactam has been established in the clinical setting for some time and is effective against a number of ß-lactamase-producing strains of Staphylococcus aureus and some Enterobacteriaceae, and against Bacteroides fragilis and ß-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis (~70% of strains of this organism produce ß-lactamases).

Penicillin G is effective only against Gram-positive bacteria, in contrast to ampicillin. Penicillin G shows two- to four-fold greater activity against susceptible Gram-positive bacteria than ampicillin. However, without the use of ß-lactamase inhibitors, ~70–80% of our S. aureus strains are resistant to penicillin. Thus, compared with penicillin G on its own, the combination penicillin G/sulbactam promises improved activity against staphylococci.

Ampicillin has a broad spectrum of activity, and is also effective against enterococci and some Gram-negative organisms. However, with the exception of H. influenzae and M. catarrhalis, Gram-negative bacteria do not play an important role in ENT infections. On the basis of these theoretical considerations, utilization of penicillin G in combination with sulbactam may present an effective alternative in the treatment of ENT infections. We conducted a study to compare the activity of penicillin G (Grünenthal, Aachen, Germany) in combination with sulbactam (Pfizer, Karlsruhe, Germany) against common organisms of ENT infections, with the activity of penicillin G, cefotiam (Grünenthal, Germany), clindamycin (Pharmacia & Upjohn GmbH, Erlangen, Germany) and levofloxacin (Hoechst Marion Roussel, Bad Soden, Germany). The MICs for 50 clinical isolates of methicillin-susceptible S. aureus (MSSA), Streptococcus pyogenes, M. catarrhalis and H. influenzae were determined by a microdilution technique according to NCCLS guidelines.1 S. aureus ATCC 29213, H. influenzae ATCC 49247 and M. catarrhalis ATCC 43617 were used as reference strains.

Table Go shows the MIC distribution of all the antibiotics tested for the different bacteria. Pencillin G/sulbactam showed high-level activity against all the bacteria tested. The combination of pencillin G and sulbactam reduced the MIC90 for S. aureus and H. influenzae from 1 to 0.06 mg/L and from 2 to 0.25 mg/L, respectively. The MIC90 for M. catarrhalis was also decreased from 8 to <=0.004 mg/L, whereas there was no difference in the activity of penicillin G against S. pyogenes (MIC90 = 0.008 mg/L).


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Table 1.  In vitro activity (MIC in mg/L) of various antibiotics against S. aureus, S. pyogenes, M. catarrhalis and H. influenzae  
 
There are few data in the literature on the antimicrobial in vitro activity of penicillin G/sulbactam. Jansen et al.2 reported excellent antimicrobial activity for pencillin G/sulbactam against MSSA compared with ampicillin/sulbactam, co-amoxiclav, piperacillin/tazobactam and oxacillin, and demonstrated that the combination pencillin G/sulbactam restored the susceptibility of penicillinase-producing strains of MSSA. Our results corroborate these findings. Furthermore, in our investigation we were able to show that susceptibility of important pathogens causing common ENT infections is improved. Clinical trials should be conducted to investigate further the clinical efficacy of this drug combination in oral or parenteral preparations.

Acknowledgements

This study was sponsored by Pfizer GmbH, Karlsruhe, Germany

Footnotes

* Corresponding author. Tel: +49-761-270-5478; Fax: +49-761-270-5486; E-mail: swenzler{at}iuk3.ukl.uni-freiburg.de Back

References

1 . National Committee for Clinical Laboratory Standards. (1998). Performance Standards for Antimicrobial Susceptibility Testing—Eighth Informational Supplement M100-S8. NCCLS, Villanova PA, USA.

2 . Jansen, B., Perdreau-Remington, F. & Pulverer G. (1996). In-vitro activity of penicillin G plus sulbactam in comparison with other ß-lactamase inhibitor combinations and oxacillin against staphylococci. Zentralblatt für Bakteriologie 284, 297–301.[ISI][Medline]





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