Comparative Antibacterial Activity of the Penem ALP 201

In vitro susceptibility of 185 penicillin-susceptible and -resistant pneumococci to WY-49605, a new oral penem, was compared with susceptibility to penicillin G, amoxicillin with and without clavulanate, cefixime, cefaclor, cefpodoxime, cefuroxime, and cefdinir. WY-49605 yielded MICs for 50 and 90%o of the strains tested (MIC50 and MIC90, respectively) of 0.03 and 0.06, 0.125 and 0.5, and 0.5 and 1.0 ,ug/ml, respectively, against penicillin-susceptible, intermediately resistant, and fully resistant strains, respectively. The MIC50 and MIC90for both amoxicillin and amoxicillin-clavulanate were identical and approximately 1 doubling dilution higher than those for WY-49605 and were .0.06 and 0.125, 0.25 and 1.0, and 1.0 and 1.0 ,ug/ml, respectively. Cephalosporin MIC90s were all significantly higher than those of the latter three compounds for intermediately resistant and fully resistant strains.

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confidence: 99%

In vitro susceptibilities of 185 penicillin-susceptible and -resistant pneumococci to WY-49605 (SUN/SY 5555), a new oral penem, compared with those to penicillin G, amoxicillin, amoxicillin-clavulanate, cefixime, cefaclor, cefpodoxime, cefuroxime, and cefdinir

Spangler

Jacobs

Appelbaum

1994

“…WY-49605 (previously SUN5555, SY5555, or ALP-201) is an orally administered penem that exhibits a broad in vitro antibacterial spectrum against both anaerobic and aerobic bacteria (1,(4)(5)(6). It has also been shown to be highly resistant to the actions of a variety of ␤-lactamase enzymes (1,4).…”

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confidence: 99%

“…It has also been shown to be highly resistant to the actions of a variety of ␤-lactamase enzymes (1,4).…”

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confidence: 99%

Antibacterial activity of WY-49605 compared with those of six other oral agents and selection of disk content for disk diffusion susceptibility testing

Fuchs

Barry

Sewell

1995

The in vitro antimicrobial activity of an oral penem, WY-49605, was compared with those of six other oral antimicrobial agents against 598 bacterial isolates representing 51 different species. WY-49605 exhibited good activity against most gram-positive bacteria and members of the family Enterobacteriaceae. It had little activity against nonfermenting gram-negative bacilli, Enterobacter spp., Serratia spp., enterococci, Staphylococcus haemolyticus, and methicillin-resistant Staphylococcus aureus. Its activity was unaffected by the ␤-lactamases of Neisseria gonorrhoeae, Haemophilus influenzae, and staphylococci. Disk diffusion susceptibility tests were performed with 5-, 10-, 15-, and 30-g WY-49605 disks. The 5-g disk is recommended, with tentative breakpoints of >16 mm for susceptibility (MIC, <2.0 g/ml) and <12 mm for resistance (MIC, >8.0 g/ml). SY5555, is an orally administered penem that exhibits a broad in vitro antibacterial spectrum against both anaerobic and aerobic bacteria (1, 4-6). It has also been shown to be highly resistant to the actions of a variety of ␤-lactamase enzymes (1, 4). WYIn this report, we describe the results of two separate studies. The first study compared the in vitro antibacterial activity of WY-49605 with those of six other oral antibiotics currently available in the United States against a wide range of bacterial isolates. A second study determined the optimal disk content of WY-49605 for disk diffusion susceptibility testing. MATERIALS AND METHODSIn the first study, 598 stock cultures that had been derived from clinical specimens over the past 15 years were selected to represent the 51 different species that are listed in Table 1. WY-49605 was provided as a standardized powder by Wyeth-Ayerst Research, Philadelphia, Pa. The drugs used for comparison, amoxicillin, amoxicillin-clavulanate, cefaclor, cefuroxime, cefixime, and ciprofloxacin, were procured from their respective U.S. manufacturers. Susceptibility tests were performed by the broth microdilution method outlined by the National Committee for Clinical Laboratory Standards (NCCLS) (2). The antibiotic concentrations tested were serial twofold dilutions ranging from 16 to 0.03 g/ml for all drugs except ciprofloxacin, which was tested at concentrations of from 4.0 to 0.008 g/ml.In the second study, 490 bacterial isolates representing 32 different species were selected from the first culture collection for which there was a wide range of WY-49605 MICs. The week before the second study was initiated, filter paper disks were prepared at the Clinical Microbiology Institute to contain WY-49605 at 110% of the following potencies: 5, 10, 15, and 30 g. The compound has been shown to be stable for up to 2 years at room temperature (7), and there was no change in zone diameters with control strains for the duration of the study. Commercially prepared 30-g ceftriaxone disks (lot no. 204657; B-D Microbiology Systems) were also tested for control purposes. Disk diffusion susceptibility tests were performed with all five disks as outlined...

“…Its chemical structure has been described by Nishino and coworkers as sodium (5R, 6S, 8R, 2'R)-2-(2'-tetrahydrofuryl)-6-hydroxyethylpenem-3-carboxylate (18). This compound is stable to most classes of ,B-lactamases and seems less epileptogenic than impinenem (11,14,15,18,(20)(21)(22)24 Metronidazole had an MIC50 of 2.0 ,ug/ml and an MIC90 of 16.0 j,g/ml against all strains. All gram-negative strains yielded MICs of s4.0 ,ug/ml; only gram-positive non-spore-forming anaerobic rods, some peptostreptococci, and some clostridia yielded MICs of >8.0 ,ug/ml.…”

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confidence: 99%

“…Results of anaerobic gram-negative rods, broken down according to ,-lactamase production, are presented in Table 2 (11,14,15,18,(20)(21)(22)24). Although lacking in activity against Pseudomonas species, WY-49605 is much more potent against staphylococci (methicillin susceptible), streptococci, and most gram-negative organisms (including Haemophilus influenzae, Neisseria gonorrhoeae, and Moraxella catarrhalis) than other oral ,-lactams such as cefaclor, cefixime, and amoxicillin (18 cephalosporins (18).…”

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confidence: 99%

Activity of WY-49605 compared with those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 anaerobic bacteria

Spangler

Jacobs

Appelbaum

1994

The National Committee for Clinical Laboratory Standards agar dilution method was used to compare the in vitro activity of WY-49605 (also called SUN/SY 5555 and ALP-201), a new broad-spectrum oral penem, to those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 clinically isolated anaerobes. These anaerobic organisms included 90 strains from the Bacteroides fragilis group, 87 PrevoteUla and Porphyromonas strains, non-B. fragilis group Bacteroides strains, 56 fusobacteria, 55 peptostreptococci, 49 gram-positive non-spore-forming rods, and 47 clostridia. Overall, VVY-49605 had an MIC range of 0.015 to 8.0 ,ig/ml, an MIC at which 50% of the isolates are inhibited (MIC50) of 0.25 ,ig/ml, and an MIC at which 90% of the isolates are inhibited (MIC90) of 2.0 ,ug/ml. Good activity against all anaerobe groups was observed, except for Clostridium diJficik and lactobacilli (MIC,0s of 4.0 and 2.0 ,ug/ml, respectively, and MIC90s of 8.0 and 2.0 ,ug/ml, respectively). Imipenem had an MWIC50 of 0.03 ,ug/ml and an MIC90 of 0.25 ,Lg/ml. Ciprofloxacin was much less active (MIC_o of 2.0 ,ug/ml and MIC90 of 16.0 ,ug/ml). By comparison, all oral ,I-lactams were less active than WY-49605, with susceptibilities as follows: amoxicillin MIC_o of 8.0 ,Ig/ml and MIC90 of >256.0 ,ug/ml), amoxicillin-clavulanate MIC50 of 1.0 ,Ig/ml and MIC90 of 8.0 ,ug/ml, cefaclor MIC50 of 8.0 ,ug/ml and MIC90 of >32.0 ,ug/ml, cefpodoxime MIC_0 of 4.0 ,ug/ml and MIC90 of >32.0 ,ug/ml, and cefuroxime MIC50 of 4.0 ,ug/ml and MIC90 of >32.0 jig/ml.Clindamycin was active against all groups except some members of the B.fragilis group, Fusobacterium varium, and some clostridia (overall MIC50 of 0.5 ,ug/ml and overall MIC90 of 8.0 ,ug/ml). Metronidazole was active (MIC of <4.0 ,Ig/ml) against all gram-negative anaerobic rods, but most gram-positive non-spore-forming rods, some peptostreptococci, and some clostridia were less susceptible. To date, WY-49605 is the most active oral ,-lactam against anaerobes: these results suggest clinical evaluation for clinical indications suitable for oral therapy.