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. 1987 Apr;31(4):558–569. doi: 10.1128/aac.31.4.558

In vitro activity and beta-lactamase stability of a new penem, CGP 31608.

H C Neu, N X Chin, N M Neu
PMCID: PMC174777  PMID: 3496845

Abstract

The in vitro activity of CGP 31608, a new penem, against aerobic and anaerobic organisms was evaluated and compared with those of other beta-lactams. CGP 31608 inhibited Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, Citrobacter diversus, and Salmonella, Shigella, Aeromonas, and Yersinia spp. with MICs for 50% of the strains (MIC50s) of 2 to 4 micrograms/ml and MIC90s of 4 micrograms/ml, compared with cefotaxime, ceftazidime, aztreonam, and imipenem MICs of less than 0.25 microgram/ml. MIC90s were 8 micrograms/ml for Enterobacter species and C. freundii, for which other agents had MICs of 32 micrograms/ml, except imipenem, which had equal activity. The MIC90 for Proteus vulgaris, Morganella morganii, Providencia stuartii, and Providencia rettgeri was 8 micrograms/ml, compared with less than 2 micrograms/ml shown by the other agents. Acinetobacter species resistant to other agents except imipenem were inhibited by 4 micrograms/ml, as were Pseudomonas aeruginosa, including piperacillin-, ceftazidime-, and gentamicin-resistant isolates. The MIC for P. cepacia, P. fluorescens, and P. acidovorans was less than or equal to 8 micrograms/ml, but that for P. maltophilia was greater than or equal to 128 micrograms/ml. Hemolytic streptococci A, B, C, G, and F were inhibited by less than 1 micrograms/ml, but the MIC for Streptococcus faecalis was greater than or equal to 32 micrograms/ml. MICs for Staphylococcus aureus methicillin-susceptible and -resistant strains were less than or equal to 1 microgram/ml, as were those for methicillin-susceptible and -resistant S. epidermidis. Bacteroides fragilis and Clostridium species and Fusobacterium spp. were inhibited by less than or equal to 4 micrograms/ml. CGP 31608 was not hydrolyzed by plasmid beta-lactamases TEM-1, TEM-2, SHV-1, PSE-1, OXA-2, PSE-4, or by S. aureus. Chromosomal beta-lactamases of type Ia in Enterobacter cloacae P99 and Morganella morganii, Ic in P. vulgaris, K-1 in K. oxytoca, and Id in P. aeruginosa also did not hydrolyze CGP 31608. It inhibited TEM-1, but the 50% inhibitory concentration was 14.2 micrograms/ml compared with 0.15 micrograms/ml for the P99 enzyme. CGP 31608 induced beta-lactamases in P. aeruginosa, E. cloacae, C. freundii and Providencia rettgeri, but there was no increase in MICs for the isolates and it did not select strains derepressed for beta-lactamase production. Synergy of CGP 31608 and gentamicin was found against 90% P. aeruginosa, 60% Enterobacter cloacae, and 50% Serratia marcescens strains. No synergy was found with rifampin. A postantibiotic effect was found against E. coli.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bruna C. D., Jabes D., Sebben G., Sanfilippo A. In vitro and in vivo evaluation of the penem FCE 22101 and its orally absorbed ester FCE 22891. G Ital Chemioter. 1983 May-Dec;30(2-3):125–130. [PubMed] [Google Scholar]
  2. Ganguly A. K., Afonso A., Girijavallabhan V. M., McCombie S. Synthesis and preliminary in-vitro profile of Sch 34343--a new penem antibacterial agent. J Antimicrob Chemother. 1985 Jun;15 (Suppl 100):1–4. doi: 10.1093/jac/15.suppl_c.1. [DOI] [PubMed] [Google Scholar]
  3. Kahan F. M., Kropp H., Sundelof J. G., Birnbaum J. Thienamycin: development of imipenen-cilastatin. J Antimicrob Chemother. 1983 Dec;12 (Suppl 500):1–35. doi: 10.1093/jac/12.suppl_d.1. [DOI] [PubMed] [Google Scholar]
  4. Loebenberg D., Miller G. H., Moss E. L., Jr, Oden E., Hare R. S., Chung M., Waitz J. A. Evaluation of the in-vitro activity of Sch 29482. J Antimicrob Chemother. 1982 Feb;9 (Suppl 100):221–231. doi: 10.1093/jac/9.suppl_c.221. [DOI] [PubMed] [Google Scholar]
  5. Neu H. C., Chin N. X., Labthavikul P. In-vitro activity and beta-lactamase stability and inhibitory properties of a new penem antibiotic, Sch 34343. J Antimicrob Chemother. 1985 Jun;15 (Suppl 100):25–37. doi: 10.1093/jac/15.suppl_c.25. [DOI] [PubMed] [Google Scholar]
  6. Neu H. C., Chin N. X., Labthavikul P. The in-vitro activity of a novel penem FCE 22101 compared to other beta-lactam antibiotics. J Antimicrob Chemother. 1985 Sep;16(3):305–313. doi: 10.1093/jac/16.3.305. [DOI] [PubMed] [Google Scholar]
  7. Richmond M. H., Clark D. C., Wotton S. Indirect method for assessing the penetration of beta-lactamase-nonsusceptible penicillins and cephalosporins in Escherichia coli strains. Antimicrob Agents Chemother. 1976 Aug;10(2):215–218. doi: 10.1128/aac.10.2.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Richmond M. H., Sykes R. B. The beta-lactamases of gram-negative bacteria and their possible physiological role. Adv Microb Physiol. 1973;9:31–88. doi: 10.1016/s0065-2911(08)60376-8. [DOI] [PubMed] [Google Scholar]
  9. Sanders C. C., Sanders W. E., Jr Emergence of resistance during therapy with the newer beta-lactam antibiotics: role of inducible beta-lactamases and implications for the future. Rev Infect Dis. 1983 Jul-Aug;5(4):639–648. doi: 10.1093/clinids/5.4.639. [DOI] [PubMed] [Google Scholar]
  10. Wise R., Andrews J. M., Danks G. Comparison of in vitro activity of FCE 22101, a new penem, with those of other beta-lactam antibiotics. Antimicrob Agents Chemother. 1983 Dec;24(6):909–914. doi: 10.1128/aac.24.6.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Zimmermann W. Penetration through the gram-negative cell wall: a co-determinant of the efficacy of beta-lactam antibiotics. Int J Clin Pharmacol Biopharm. 1979 Mar;17(3):131–134. [PubMed] [Google Scholar]

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