ANTIMICROBIAi, AGENTS AND CHEMOTHERAPY, OCt. 1981, I). 553-555 Vol. 20, No. 4 0066-4804/81/ 100553-0:3$02.00/() Susceptibility of Gram-Positive Cocci to Various Antibiotics, Including Cefotaxime, Moxalactam, and N-Formimidoyl Thienamycin CHARLES E. CHERUBIN,'* MICHAEL L. CORRAI)O,2 MARCELINO F. SIERRA, MYLES E. GOMBERT,2 AND) MICHAEL SHULMAN' The Infectious Disease Service, Brooklyn -Jewish Hospital, Brooklyn, Newl York 112,381; and The Infectious Disease Division2 and The Department of Pathology, 3Downstate Medical Center, State Jniversity of New York, Brooklyn, New York 11203 Received 27 March 1981/Accepted 25 June 1981 The activities of cefotaxime, moxalactam, MK 0787 (N-formimidoyl thiena- mycin), ampicillin, oxacillin, vancomycin, and clindamycin were compared against gram-positive cocci. MK 0787 was the most active and moxalactam was the least active of these drugs, except against methicillin-resistant Staphylococcus aureus, where vancomycin was most active, and penicillin-resistant pneumococci, where cefotaxime was more active. A number of beta-lactam antibiotics with Laboratories), vancomycin (Eli Lilly & Co.), clin- broadened coverage and enhanced activity damycin (The Upjohn Co.), cefotaxime against gram-negative bacilli have been devel- (Hoechst Roussel Pharmaceuticals, Inc.), and oped recently (2, 6, 8-10). If these compounds cephalothin (Eli Lilly & Co.) in sterile water possess high activity against common gram-pos- (6,400 fig/ml) and moxalactam (Eli Lilly & Co.) itive pathogens, they might be considered for in 1 M phosphate buffer (pH 7; 6,400 tig/ml) empirical use as the sole therapeutic agent until were stored at -70°C until used. N-Formimidoyl identification and susceptibility reports on cul- thienamycin (MK 0787) (Merck & Co., Inc.) was ture specimens are obtained. We report herein prepared daily in sterile water (2,560 tig/ml). the results of a comparison of the activities of The preparation of the inocula and definitions three relatively new beta-lactams, cefotaxime, of the minimum inhibitory and minimum bac- moxalactam, and MK 0787 (N-formimidoyl tericidal concentrations (MIC and MBC, respec- thienamycin), as well as oxacillin, ampicillin, tively) have previously been described (3). Using vancomycin, and clindamycin, against gram-pos- the microtiter system, we performed susceptibil- itive bacteria associated with endocarditis and ity testing for all isolates except methicillin-re- bacteremia. sistant staphylococci (3). Methicillin-resistant The 157 isolates examined in this study were staphylococci were tested by a broth macrotiter obtained from patients with diagnosed endocar- method also previously described (3), as well as ditis, intravascular catheter-associated bactere- the microtiter method, which was read at 24 and mia, cellulitis, pneumonia, neonatal bacteremia 48 h. Mueller-Hinton broth (MHB; BBL Micro- and meningitis, hepatic abscess, cholangitis, and biology Systems) was utilized for all tests except bacteremias of obscure origin. All isolates except those on the beta-hemolytic streptococci and S. the penicillin-resistant pneumococci were ob- pneumoniae, where MHB supplemented by 10% tained from multiple (two or more) blood cul- laked sheep's blood was utilized. Inocula of 5 x tures from patients at the Brooklyn Jewish, 10" colony-forming units per ml and 5 x 10' Kings County, and State University hospitals. colony-forming units per ml were used in suscep- The resistant pneumococci, obtained from Har- tibility testing of all isolates except the beta- riet Bernheimer, had been isolated from blood hemolytic streptococci and S. pneumoniae, and spinal fluid of South African patients. The where only the 5 x 10' colony-forming units per beta-hemolytic streptococci were grouped by ml inoculum was tested. both the Phadebact agglutination and autoclave At the MIC.,1 level, MK 0787 was either equiv- precipitation extraction methods (7). Identifica- alent in activity or more active than any other tion of each isolate was performed by conven- compound tested against each group of isolates, tional methods (1, 4, 5). except the methicillin-resistant Staphylococcus Antibiotics. Stock solutions of oxacillin aureus, where vancomycin was most active, and (Bristol Laboratories), ampicillin (Beecham the penicillin-resistant S. pneumoniae, where 5513 554 NO<I'ES ANTIMICROB. A(GFNTS CHFMOTHER. TABLE 1. MICs of variolus compounds against gram -positivte coccii Compound Range of MICS MI( Isolate (no.) (pg/mi of mnedIiunm) Group A streptococci ( 11) Oxacillin 0.03-0.5 0.06 0.15 Ampicillin <0.03-0.06 <0.0:3 0.06 Vancomwcin <0.03-0.25 <0.03 0.25 Clindanivcin <0(.3-0.25 0.06 0.06 Cefotaxime <0.03-0.125 0.06 0.125 Moxalactam 0.5-2 MK 0787 <(.0 1 -0.06 <().(). 0.06 Group B streptococci (8) Oxacillin 0.03-0.5 0.06 (0.5 0.06 (0.125 Ampicillin <().0.3-0.125 ().()( Vancomycin <t).03-0. 125 0.06 (0.125 Clindanwcin 0.06-0.5 ((.5 Cefotaxime <().0:3-0.25 (0.25 Moxalactamn 2-4 4 MK (n787 <0.0 1 -(0.0:3 0.06 Gro)up C and G streptococci (6) Oxacillinl 0.0:3-0.5 0.06 Ampicillin <0.0:3-0.25 ((.063 (0.25 Vanconivcill 0.06-0.5 0.0:3 (0.25 Clindamnvcin <().03-0.5 (0.125 Cefotaxime <0(.0:3-0. 125 (0.125 Moxalactam 2-8 <0.06 8 MK ((787 <0.0 1 <0.06 (.0 1 Str-eptococcus faecalis (:3 1) Cephalothin 8-:32 1 6 :32 Ampicillinl <(0.5-) <(0.5 <0.5 \ancomrycin <0.5-1 ().(); 1 Clindamnvcin 4-64 .32 Cefotaxime 8->16 >16 Moxalactam 16->16 <0.53 >16 MK 0787 0.125-0.5 ((.5 Viridans streptococci (17) Oxacillinl <(0.03-0.06 ().()t Ampicillin <(0((3-0.25 t).25 Vancomrcin <0.03-0.5 ((.125 0.25 Clindarnvcin <0.03-0.5 0.06 0).06 Cefotaxime <0.03-0.5 0).125 Moxalactam 0.5-2 MK 0787 <(0( 1 <((1 <(). 19 1) S. pneum0nilae, penicillin suscep- Oxacillinl 0).03-0.25 (0.125 tible (10) Ampicillin <0.03-0.125 <(.0(3 Vancomncin 0.5-2 0.0(6 Clindamycin <0.03-0). 125 <0.0:3 (0.125 Cefotaxinie <().03-0. 125 <().() 1 Moxalactam (0.06-(0.5 0.5 (0.5 MK 0787 <(0.01 <().()1 S. pneumoniae, penicillin resist- Oxacillinl 1->8 >8 ant (10) Ampicillin 1 ->8 <0.01 8 Vancomvcin 0.125-2 -::8 2 Clindamnycin 0.25-,8 Cefotaxime 0.125-0.5 t(.5 Moxalact am o.5-,8 (0.25 1 -1 MK 0787 ().( 58 Staphylococcus epidlermic/is (3() Oxacillinl 0. 125->16 ((.5 8 Ampicillin <0. 125-> 16 0.5 8 Vanconmcvin '2->16 8 Clindamvcin 0. 125->16 16 Cef'otaxinie ().06-> 16 4 I 6 VOL. 20, 1981 NOTES 555 TABLE 1.-Continued Isolate (no.) Range of MICs (Cug/ml of medium) Moxalactam 1->16 8 >16 MK 0787 <0.01->16 0.03 2 S. aureus, methicillin susceptible Oxacillin 0.125-1 0.25 0.5 (20) Ampicillin 32->32 >32 >32 Vancomycin <0.125-0.5 0.25 0.5 Clindamycin <0.125 <0.125 <0.125 Cefotaxime 0.125-2 1 1 Moxalactam 4-8 4 4 MK 0787 <0.01 <0.01 <0.01 S. aureus, methicillin resistant Oxacillin 32-128 32 32 (14) Ampicillin 8->64 32 32 Vancomycin 0.5-2 0.5 1 Clindamycin 32->64 >64 >64 Cefotaxime 8->64 >64 >64 Moxalactam >64 >64 >64 MK 0787 0.01-8 0.03 4 " MIC5) and MIC%,, MIC for 50 and 90%, respectively, of the isolates. cefotaxime was most active (Table 1). Moxalac- Gorbach. 1979. In vitro activity of LY 127935. Anti- tam, on the other hand, was either the least microb. Agents Chemother. 16:287-291. 3. Corrado, M. L., S. H. Landesman, and C. E. Cherubin. active or among the least active of the drugs 1980. Influence of inoculum size on activity of cefoper- against all isolates tested. Among drugs which azone, cefotaxime, piperacillin and N-fornmimidoyl are either beta-lactamase resistant or relatively thienamycin (MK 0787) against Pseudomonas aerlugi- so, moxalactam displayed least activity against nosa. Antimicrob. Agents Chemother. 18:893-896. 4. Facklam, R. R. 1974. Streptococci, p. 96-108. In E. H. methicillin-susceptible S. aureus. Lennette, E. H. Spaulding, and J. P. Truant (ed.), The MBCs were generally identical to the Manual of clinical microbiology, 2nd ed. American So- MIC or were only twofold higher for all drugs ciety for Microbiology, Washington, D.C. against each of the various isolates. Increasing 5. Ivler, D. 1974. Staphylococcus, p. 91-95. In E. H. Len- the inoculum to 5 x nette, E. H. Spaulding, and J. P. Truant (ed.), Manual 10' colony-forming units per of clinical microbiology, 2nd ed. American Society for ml did not significantly alter the MBCs except Microbiology, Washington, D.C. against staphylococci. There was a fourfold in- 6. Neu, H. C., N. Aswapokee, K. P. Fu, and P. Aswa- crease in the MBCs for vancomycin in 14 of 20 pokee. 1979. Antibacterial activity of a new 1-oxa ceph- alosporin compound with that of other beta-lactam isolates of aureus, methicillin-susceptible S. in compounds. Antimicrob. Agents Chemother. 16:141- 7 of 20 for clindamycin, and in 4 of 20 for 149. cefotaxime. Similar trends were seen with coag- 7. Rantz, L. A., and E. Randall. 1955. Use of autoclaved ulase-negative staphylococci for oxacillin, ampi- extracts of haemolytic streptococci for serological cillin, grouping. Stanford Med. Bull. 13:290-291. cefotaxime, and, occasionally, for MK 8. Tally, F. P., N. V. Jacobus, and S. L. Gorbach. 1978. 0787. In vitro activity of thienamycin. Antimicrob. Agents LITERATURE CITED Chemother. 14:436-438. 9. Verbist, L., and J. Verhaegen. 1981. In vitro activity of 1. Austrian, R. 1974. Streptococcus pneumoniae (pneumo- Ro 13-9904, a new beta-lactamase-stable cephalosporin.