Skip to main page content

• HOME
• Current Issue
• Archive
• Alerts
• About ASM
• Contact us
• Tech Support
• Journals.ASM.org

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sader, H. S. Articles by Jones, R. N. Search for Related Content PubMed PubMed Citation Articles by Sader, H. S. Articles by Jones, R. N.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2004, p. 53-62, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.53-62.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of the Novel Cephalosporin LB 11058 against Multidrug-Resistant Staphylococci and Streptococci

Helio S. Sader,^1,2* David M. Johnson,¹ and Ronald N. Jones^1,3

The JONES Group/JMI Laboratories, North Liberty, Iowa,¹ Universidade Federal de São Paulo, São Paulo, Brazil,² Tufts University School of Medicine, Boston, Massachusetts³

Received 5 June 2003/ Returned for modification 7 August 2003/ Accepted 3 October 2003

Top Abstract Introduction Materials and Methods Results Discussion References

 
LB 11058 is a novel parenteral cephalosporin with a C-3 pyrimidinyl-substituted vinyl sulfide group and a C-7 2-amino-5-chloro-1,3-thiazole group. This study evaluated the in vitro activity and spectrum of LB 11058 against 1,245 recent clinical isolates, including a subset of gram-positive strains with specific resistant phenotypes. LB 11058 was very active against Streptococcus pneumoniae. The novel cephalosporin was 8- to 16-fold more potent than ceftriaxone, cefepime, or amoxicillin-clavulanate against both penicillin-intermediate and -resistant S. pneumoniae. LB 11058 was also very active against both ß-hemolytic streptococci (MIC at which 90% of isolates were inhibited [MIC₉₀], 0.008 µg/ml) and viridans group streptococci (MIC₉₀, 0.03 to 0.5 µg/ml), including penicillin-resistant strains. Among oxacillin-susceptible Staphylococcus aureus, LB 11058 MIC results varied from 0.06 to 0.25 µg/ml (MIC₅₀, 0.12 µg/ml), while among oxacillin-resistant strains LB 11058 MICs varied from 0.25 to 1 µg/ml (MIC₅₀, 1 µg/ml). Coagulase-negative staphylococci showed an LB 11058 susceptibility pattern similar to that of S. aureus, with all isolates being inhibited at 1 µg/ml. LB 11058 also showed reasonable in vitro activity against Enterococcus faecalis, including vancomycin-resistant strains (MIC₅₀, 1 µg/ml), and Bacillus spp. (MIC₅₀, 0.25 µg/ml); however, it was less active against Enterococcus faecium (MIC₅₀, >64 µg/ml) and Corynebacterium spp. (MIC₅₀, 32 µg/ml). Against gram-negative pathogens, LB 11058 showed activity against Haemophilus influenzae (MIC₉₀, 0.25 to 0.5 µg/ml) and Moraxella catarrhalis (MIC₉₀, 0.25 µg/ml), with MICs not influenced by ß-lactamase production. In conclusion, LB 11058 demonstrated a broad antibacterial spectrum and was highly active against gram-positive bacteria, particularly against multidrug-resistant staphylococci and streptococci.

Top Abstract Introduction Materials and Methods Results Discussion References

 
Gram-positive bacterial pathogens have shown a remarkable ability to develop resistance to antimicrobial agents. Oxacillin- and glycopeptide-resistant staphylococci, glycopeptide-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae and viridans streptococci have forced clinicians to seek alternative treatments for patients with serious gram-positive infections (1, 2, 3, 11, 15, 16).

Oxacillin-resistant Staphylococcus aureus (MRSA) represents an important worldwide problem, and its prevalence may vary significantly from hospital to hospital. Data from the global SENTRY Antimicrobial Surveillance Program and other surveillance programs revealed a high and increasing prevalence of this pathogen in the United States, Latin America, and several regions of Europe (5; European Antimicrobial Resistance Surveillance System [http://www.earss.rivm.nl], accessed 24 September 2003). Over the past few years, MRSA has acquired stable resistance to most clinically available antimicrobial agents, and therapeutic options have been limited to the glycopeptides (vancomycin and teicoplanin) and, more recently, quinupristin-dalfopristin and linezolid (4, 7). However, clinical isolates with reduced susceptibilities to these latter compounds have recently been described in several regions of the world (5, 7, 13). Most MRSA isolates show resistance to virtually all ß-lactams by production of penicillinase and a low-affinity penicillin-binding protein (PBP) called PBP 2a. ß-Lactams with relatively high affinities for PBP 2a, such as penicillin, ampicillin, and amoxicillin, combined with ß-lactamase inhibitors have demonstrated in vitro and in vivo anti-MRSA activities (10). However, the addition of critical amounts of ß-lactamase inhibitor are necessary to successfully treat these infections. Thus, ß-lactams must combine both high affinity for PBP 2a and stability against degradation by staphylococci penicillinase to be considered for clinical use against infections caused by this pathogen (2, 12).

S. pneumoniae is the most commonly identified bacterial cause of community-acquired pneumonia, otitis media, and meningitis, and it is a frequent pathogen in bacteremia (6, 21). Morbidity and mortality may be high among patients with bacteremia and meningitis, especially when appropriate antimicrobial therapy is delayed. The emergence of S. pneumoniae with antimicrobial resistance has also become a matter of major concern. Resistance to penicillin and other antimicrobial agents has increased significantly in the last decade, making the treatment of serious infections very difficult, especially among children (15, 16, 19, 20, 22).

LB 11058 is a novel parenteral cephalosporin with a C-3 pyrimidinyl-substituted vinyl sulfide group and a C-7 2-amino-5-chloro-1,3-thiazole group (Fig. 1). Preliminary studies have indicated that this compound has potent in vitro activity against gram-positive bacteria, including multidrug-resistant staphylococci and streptococci. This study was designed to confirm and extend the earlier presentations about the potency and spectrum of LB 11058 (Y. Cho, M. Kim, C. S. Lee, and H. Youn, 42nd Intersci. Conf. Antimicrob. Agents Chemother., abstr. F-330, 2002; H. Joo, J. E. Shin, I. H. Choi, D. H. Park, S. H. Kim, S. H. Lee, and H. Youn, 42nd Intersci. Conf. Antimicrob. Agents Chemother., abstr. F-331, 2002; C. Lee, Y. Jang, K. Koo, Y. Cho, 42nd Intersci. Conf. Antimicrob. Agents Chemother., abstr. F-329, 2002).

View larger version (8K): [in this window] [in a new window]

FIG. 1. Chemical structure of LB 11058.

Top Abstract Introduction Materials and Methods Results Discussion References

 
Antimicrobials tested. The LB 11058 reagent-grade compound was provided by LG Life Science, Ltd. (Taejon, South Korea). Comparator agents were purchased from Sigma Chemical Co. (St. Louis, Mo.) or obtained from their respective manufacturers in the United States. A total of 31 comparators were evaluated, depending upon the species tested. These compounds included ß-lactams (penicillins, cephalosporins, penicillin-ß-lactamase inhibitor combinations, a monobactam, and a carbapenem), fluoroquinolones, aminoglycosides, trimethoprim-sulfamethoxazole, and several gram-positive-focused agents (macrolide-lincosamide-streptogramins, glycopeptides, and oxazolidinones).

Organisms tested. A total of 1,245 well-characterized strains derived from numerous laboratories worldwide, including a subset of gram-positive strains with specific resistant phenotypes, were processed in the study. Only nonduplicate isolates judged to be clinically significant by local criteria were included in the study. All isolates were collected in 2002, except some isolates of the multidrug-resistant subset. The collection of organisms included 102 isolates of ß-hemolytic streptococci, 205 S. pneumoniae isolates (103 penicillin nonsusceptible), 106 isolates of viridans group streptococci (54 penicillin nonsusceptible), 163 S. aureus isolates (110 MRSA), 101 coagulase-negative staphylococci (CoNS; 76 oxacillin resistant), 64 Enterococcus faecalis isolates (20 vancomycin resistant), 63 Enterococcus faecium isolates (33 vancomycin resistant), 17 Enterococcus spp. isolates, 20 Bacillus spp. isolates, 20 Corynebacterium spp., 203 Haemophilus influenzae isolates (101 ß-lactamase positive), 102 Moraxella catarrhalis isolates, 31 Enterobacteriaceae isolates, and 12 isolates of nonfermentative gram-negative bacilli. The subsets of multidrug-resistant gram-positive strains included six staphylococci with elevated vancomycin MICs (vancomycin-intermediate or -resistant staphylococci), 10 linezolid-nonsusceptible strains, and 20 quinupristin-dalfopristin (Synercid)-nonsusceptible strains.

Susceptibility testing methods. LB 11058 MICs were determined by the reference methods according to procedures recommended by the National Committee for Clinical Laboratory Standards (NCCLS) (17, 18). On each day of testing, a fresh stock solution (1,280 µg/ml) of LB 11058 was prepared and then serially diluted for a testing concentration range of 0.008 to 64 µg/ml. Supplemented 5% lysed horse blood was added for testing Streptococcus spp. and Corynebacterium spp., and Haemophilus test medium was utilized for testing H. influenzae. The MICs were interpreted according to NCCLS criteria (18). Quality control was monitored using the following organisms: S. pneumoniae ATCC 49619, E. faecalis ATCC 29212, S. aureus ATCC 29213, Escherichia coli ATCC 25923, and Pseudomonas aeruginosa ATCC 27853.

Top Abstract Introduction Materials and Methods Results Discussion References

 
The in vitro activities of LB 11058 in comparison to numerous other antimicrobial agents against gram-positive bacteria are summarized in Table 1. LB 11058 was very potent against ß-hemolytic streptococci, with all strains being inhibited at 0.015 µg/ml (MIC at which 90% of isolates were inhibited [MIC₉₀], 0.008 µg/ml). LB 11058 was the most potent compound tested against S. pneumoniae. Against S. pneumoniae, LB 11058 activity varied according to the susceptibility to penicillin. Penicillin-susceptible strains (MIC₉₀, 0.008 µg/ml) were very susceptible to LB 11058, while penicillin-intermediate strains (MIC₉₀, 0.06 µg/ml) and penicillin-resistant strains (MIC₉₀, 0.12 µg/ml) showed slightly higher LB 11058 MIC results (0.06 to 0.25 µg/ml). The novel cephalosporin was 8- to 16-fold more potent than ceftriaxone, cefepime, or amoxicillin-clavulanate against both penicillin-intermediate and -resistant strains. Penicillin-susceptible strains were very susceptible to LB 11058 and most antimicrobial agents evaluated, except for the macrolides (92.2 to 93.1% susceptible).

View this table: [in this window] [in a new window]

TABLE 1. Antimicrobial activities of LB 11058 and selected comparison drugs tested against gram-positive species

Similarly to S. pneumoniae, the susceptibilities of viridans group streptococci to LB 11058 varied according to the penicillin susceptibility. LB 11058 MICs ranged from 0.008 to 0.12 µg/ml (MIC₉₀, 0.03 µg/ml) among penicillin-susceptible isolates and from 0.03 to 1 µg/ml (MIC₉₀, 0.5 µg/ml) among penicillin-resistant strains. LB 11058 was also the most potent compound tested against viridans group streptococci, being 16-fold more potent than ceftriaxone or cefepime against this pathogen (Table 1).

LB 11058 showed potent in vitro activity against S. aureus, including oxacillin-resistant strains. Among oxacillin-susceptible strains, LB 11058 MIC results varied from 0.06 to 0.25 µg/ml (MIC₉₀, 0.25 µg/ml), while MRSA LB 11058 MICs ranging from 0.25 to 1 µg/ml (MIC₉₀, 1 µg/ml). LB 11058 (MIC₅₀, 0.12 µg/ml) was 32-fold more potent than ceftriaxone (MIC₅₀, 4 µg/ml), 16-fold more potent than cefepime (MIC₅₀, 2 µg/ml), and 4-fold more potent than oxacillin (MIC₅₀, 0.5 µg/ml) against oxacillin-susceptible isolates; only LB 11058 (MIC₉₀, 1 µg/ml), trimethoprim-sulfamethoxazole (MIC₉₀, 1 µg/ml), vancomycin (MIC₉₀, 2 µg/ml), quinupristin-dalfopristin (MIC₉₀, 0.5 µg/ml), and linezolid (MIC₉₀, 2 µg/ml) showed reasonable in vitro activities against oxacillin-resistant strains.

CoNS showed an LB 11058 susceptibility pattern similar to that shown by S. aureus, with all isolates being inhibited at 1 µg/ml. LB 11058 (MIC₉₀, 0.12 µg/ml) was 32-fold more potent than ceftriaxone (MIC₉₀, 4 µg/ml) and 16-fold more potent than cefepime (MIC₉₀, 2 µg/ml) against oxacillin-susceptible CoNS strains. It was also very active against oxacillin-resistant strains (MIC₉₀, 0.5 µg/ml).

LB 11058 and ampicillin were the most active ß-lactams evaluated against E. faecalis. Most E. faecalis isolates showed LB 11058 MICs of 4 µg/ml, except for one isolate which was also resistant to linezolid and showed an LB 11058 MIC of >64 µg/ml. All other cephalosporins evaluated showed poor activity against this pathogen. In general, vancomycin-resistant E. faecalis showed LB 11058 MIC results approximately fourfold higher than vancomycin-susceptible E. faecalis (MIC₅₀, 0.25 and 1 µg/ml, respectively). The activity of LB 11058 was higher against E. faecalis (MIC₉₀, 2 µg/ml) than against E. faecium (MIC₅₀, >64 µg/ml). Most E. faecium strains showed high MIC results for LB 11058 and most antimicrobial agents evaluated, except quinupristin-dalfopristin and linezolid.

LB 11058 (MIC₅₀, 0.25 µg/ml) and imipenem (MIC₅₀, 0.12 µg/ml) were the most potent ß-lactams tested against Bacillus spp. (Table 1). The vast majority of Bacillus spp. isolates (85%) had LB 11058 MICs of 0.5 µg/ml. Several other compounds showed reasonable activity against this pathogen, including clindamycin (MIC₅₀, 0.5 µg/ml), levofloxacin (MIC₅₀, 0.12 µg/ml), ciprofloxacin (MIC₅₀, 0.12 µg/ml), teicoplanin (MIC₅₀, 0.12 µg/ml), and quinupristin-dalfopristin (MIC₅₀, 0.5 µg/ml). On the other hand, Corynebacterium spp. showed decreased susceptibility to LB 11058 (MIC₉₀, >64 µg/ml) and most antimicrobial agents evaluated, except for vancomycin (MIC₉₀, 0.5 µg/ml), teicoplanin (MIC₉₀, 1 µg/ml), quinupristin-dalfopristin (MIC₉₀, 0.5 µg/ml), and linezolid (MIC₉₀, 0.5 µg/ml).

Among the special subsets of isolates selected, all vancomycin-nonsusceptible strains (MIC, 4 µg/ml) were inhibited at 1 µg of LB 11058/ml (Table 1). Also, linezolid resistance did not affect LB 11058 activity among staphylococci and streptococci. All four linezolid-resistant staphylococcal isolates had an LB 11058 MIC of 0.5 µg/ml, while the linezolid-resistant Streptococcus oralis had a very low LB 11058 MIC (0.008 µg/ml). Similarly, all quinupristin-dalfopristin-nonsusceptible staphylococci showed LB 11058 MIC results of 2 µg/ml.

LB 11058 activity against H. influenzae (MIC₉₀, 0.25 to 0.5 µg/ml) was not significantly affected by the production of ß-lactamase, and it was similar to that of cefepime (MIC₉₀, 0.12 to 0.25 µg/ml) and cefuroxime (MIC₉₀, 0.12 to 0.25 µg/ml), but inferior to ceftriaxone (MIC₉₀, 0.008 to 0.015 µg/ml). Several other compounds demonstrated potent activity against this pathogen. LB 11058 (MIC₅₀, 0.03 µg/ml) was the most potent ß-lactam tested against M. catarrhalis, followed by ceftriaxone (MIC₅₀, 0.12 µg/ml), amoxicillin-clavulanate (MIC₅₀, 0.12 µg/ml), and cefepime (MIC₅₀, 0.5 µg/ml) (Table 2).

View this table: [in this window] [in a new window]

TABLE 2. In vitro activities of LB 11058 and selected comparison drugs tested against gram-negative species

Against a small number of Enterobacteriaceae strains (31), the activity of LB 11058 varied by species, but it was generally (MIC₅₀, 2 µg/ml) inferior to that of ceftriaxone (MIC₅₀, 0.25 µg/ml), ceftazidime (MIC₅₀, 1 µg/ml), or cefepime (MIC₅₀, 0.12 µg/ml). The nonfermentative gram-negative bacilli also showed decreased susceptibility to virtually all compounds evaluated when compared to the Enterobacteriaceae (Table 2).

Top Abstract Introduction Materials and Methods Results Discussion References

 
The past decade has seen a significantly increasing problem of antimicrobial resistance among gram-positive bacteria, including multidrug-resistant staphylococci, penicillin-resistant streptococci, and vancomycin-resistant enterococci (1, 3, 5, 15, 16, 21, 22). Oxacillin resistance rates are relatively high in many hospitals worldwide, forcing the use of a glycopeptide or, more recently, linezolid as empirical therapy for suspected nosocomial-acquired staphylococcal infections. Moreover, MRSA has become increasingly described in community-acquired infections in patients who have rarely been hospitalized, raising the question whether penicillinase-resistant penicillins (oxacillin, methicillin, nafcillin, etc.) or cephalosporins should still be used for empirical therapy of community-acquired S. aureus infections (8, 14).

One of the most remarkable features of LB 11058 was its in vitro activity against oxacillin-resistant staphylococci. LB 11058 inhibited the growth of all clinical MRSA strains at 1 µg/ml, although other ß-lactam compounds were not active against those strains. Oxacillin-resistant CoNS strains (MIC₉₀, 1 µg/ml) were also very susceptible to LB 11058. In this report we confirmed the potency of LB 11058 against oxacillin-resistant staphylococci, including multidrug-resistant strains (Cho et al., 42nd ICAAC). All strains with reduced susceptibility to glycopeptides (vancomycin-intermediate or -resistant staphylococci), linezolid, and quinupristin-dalfopristin showed an LB 11058 MIC of 1 µg/ml, except for one quinupristin-dalfopristin-nonsusceptible CoNS strain which showed an LB 11058 MIC of 2 µg/ml.

S. pneumoniae and H. influenzae are the most common causes of pyogenic meningitis, community-acquired pneumonia, and otitis media (6). In addition, these pathogens also represent an important cause of nosocomial pneumonia, especially when the onset of the disease occurs within 3 to 5 days after hospital admission (19). Mortality and suppurative complications associated with these infections decrease dramatically with the rapid introduction of appropriate antimicrobial therapy (22). The clinical impact of antimicrobial resistance among these pathogens, especially S. pneumoniae, varies according to the site of infection, reflecting the degree of drug penetration to that site and the ability of the host immune response to clear the infection. Thus, antimicrobial resistance has led to treatment failure in patients with meningitis and acute otitis media. The impact of pneumococcal resistance on treatment of pneumonia has been more difficult to determine, but high-level ß-lactam or macrolide resistance has been associated with increased morbidity and longer hospital stay (16, 20).

LB 11058 showed excellent in vitro activity against pneumococci, including multidrug-resistant strains. LB 11058 (MIC₅₀, 0.25 µg/ml; MIC₉₀, 0.5 µg/ml) was many fold more potent than ceftriaxone (MIC₅₀, 4 µg/ml; MIC₉₀, 32 µg/ml) against penicillin-resistant S. pneumoniae (MIC, 2 µg/ml). In addition, LB 11058 was also highly active against H. influenzae, including ß-lactamase-producing strains (MIC₉₀, 0.25 µg/ml).

In summary, our study showed that LB 11058 is very active against many clinically important bacterial pathogens, including streptococci (ß-hemolytic, viridans group, and pneumococci), staphylococci (S. aureus and coagulase negative), H. influenzae, and M. catarrhalis among others. LB 11058 in vitro activity against these pathogens was similar to that demonstrated by other new anti-MRSA cephalosporins (2, 9, 12). Moreover, LB 11058 was highly active against multidrug-resistant gram-positive pathogens that may cause both community-acquired and hospital-acquired infections, especially MRSA and penicillin-resistant S. pneumoniae. Continued development of LB 11058 appears justified.

 
* Corresponding author. Mailing address: The JONES Group/JMI Laboratories, Inc., 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317. Phone: (319) 665-3370. Fax: (319) 665-3371. E-mail: helio-sader{at}jmilabs.com.

Top Abstract Introduction Materials and Methods Results Discussion References

 

1
1. Centers for Disease Control and Prevention. 2002. Staphylococcus aureus resistant to vancomycin: United States. Morb. Mortal. Wkly. Rep. 51:565-567.[Medline]
2
2. Chamberland, S., J. Blais, M. Hoang, C. Dinh, D. Cotter, E. Bond, C. Gannen, C. Park, F. Malouin, and M. N. Dudley. 2001. In vitro activities of RWJ-54428 (MC-02,479) against multiresistant gram-positive bacteria. Antimicrob. Agents Chemother. 45:1422-1430.[Abstract/Free Full Text]
3
3. Cormican, M. G., and R. N. Jones. 1996. Emerging resistance to antimicrobial agents in gram-positive bacteria. Enterococci, staphylococci and nonpneumococcal streptococci. Drugs 51(Suppl. 1):6-12.
4
4. Diekema, D. J., and R. N. Jones. 2001. Oxazolidinone antibiotics. Lancet 358:1975-1982.[CrossRef][Medline]
5
5. Diekema, D. J., M. A. Pfaller, F. J Schmitz, J. Smayevsky, J. Bell, R. N. Jones, M. Beach, et al. 2001. Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin. Infect. Dis. 32(Suppl. 2):S114-S132.
6
6. Dunne, M. W., C. Khurana, A. A. Mohs, A. Rodriguez, A. Arrieta, S. McLinn, J. A. Krogstad, M. Blatter, R. Schwartz, S. L. Vargas, P. Emparanza, P. Fernandez, W. M. Gooch III, M. Aspin, J. Podgore, I. Roine, J. L. Blumer, G. D. Ehrlich, and J. Chow. 2003. Efficacy of single-dose azithromycin in treatment of acute otitis media in children after a baseline tympanocentesis. Antimicrob. Agents Chemother. 47:2663-2665.[Abstract/Free Full Text]
7
7. Eliopoulos, G. M. 2003. Quinupristin-dalfopristin and linezolid: evidence and opinion. Clin. Infect. Dis. 36:473-481.[CrossRef][Medline]
8
8. Frank, A. L., J. F. Marcinak, P. D. Mangat, and P. C. Schreckenberger. 1999. Increase in community-acquired methicillin-resistant Staphylococcus aureus in children. Clin. Infect. Dis. 29:935-936.[Medline]
9
9. Fujimura, T., Y. Yamano, I. Yoshida, J. Shimada, and S. Kuwahara. 2003. In vitro activity of S-3578, a new broad-spectrum cephalosporin active against methicillin-resistant staphylococci. Antimicrob. Agents Chemother. 47:923-931.[Abstract/Free Full Text]
10
10. Hirano, L., and A. S. Bayer. 1991. ß-Lactam-ß-lactamase-inhibitor combinations are active in experimental endocarditis caused by ß-lactamase-producing oxacillin-resistant staphylococci. Antimicrob. Agents Chemother. 35:685-690.[Abstract/Free Full Text]
11
11. Jones, R. N. 2001. Resistance patterns among nosocomial pathogens. Trends over the past few years. Chest 119(2 Suppl.):397S-404S.[Abstract/Free Full Text]
12
12. Jones, R. N., L. M. Deshpande, A. H. Mutnick, and D. J. Biedenbach. 2002. In vitro evaluation of BAL9141, a novel parenteral cephalosporin active against oxacillin-resistant staphylococci. J. Antimicrob. Chemother. 50:915-932.[Abstract/Free Full Text]
13
13. Jones, R. N., P. Della-Latta, L. V. Lee, and D. J. Biedenbach. 2002. Linezolid-resistant Enterococcus faecium isolated from a patient without prior exposure to an oxazolidinone: report from the SENTRY Antimicrobial Surveillance Program. Diagn. Microbiol. Infect. Dis. 42:137-139.[CrossRef][Medline]
14
14. Jones, T. F., M. E. Kellum, S. S. Porter, M. Bell, and W. Schaffner. 2002. An outbreak of community-acquired foodborne illness caused by methicillin-resistant Staphylococcus aureus. Emerg. Infect. Dis. 8:82-84.[Medline]
15
15. Livermore, D. M. 2003. Bacterial resistance: origins, epidemiology, and impact. Clin. Infect. Dis. 36(Suppl. 1):S11-S23.[CrossRef][Medline]
16
16. Lonks, J. R., J. Garau, L. Gomez, M. Xercavins, A. Ochoa de Echaguen, I. F. Gareen, P. T. Reiss, and A. A. Medeiros. 2002. Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae. Clin. Infect. Dis. 35:556-564.[CrossRef][Medline]
17
17. National Committee for Clinical Laboratory Standards. 2003. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 6th ed. Approved document M7-A6. National Committee for Clinical Laboratory Standards, Wayne, Pa.
18
18. National Committee for Clinical Laboratory Standards. 2003. Performance standards for antimicrobial susceptibility testing, 13th informational suppl., M100-S13. National Committee for Clinical Laboratory Standards, Wayne, Pa.
19
19. Paradisi, F., G. Corti, and R. Cinelli. 2001. Streptococcus pneumoniae as an agent of nosocomial infection: treatment in the era of penicillin-resistant strains. Clin. Microbiol. Infect. 7(Suppl. 4):34-42.
20
20. Rowland, K. E., and J. D. Turnidge. 2000. The impact of penicillin resistance on the outcome of invasive Streptococcus pneumoniae infection in children. Aust. N. Z. J. Med. 30:441-449.[Medline]
21
21. Whitney, C. G., M. M. Farley, J. Hadler, L. H. Harrison, C. Lexau, A. Reingold, L. Lefkowitz, P. R. Cieslak, M. Cetron, E. R. Zell, J. H. Jorgensen, A. Schuchat, et al. 2000. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N. Engl. J. Med. 343:1917-1924.[Abstract/Free Full Text]
22
22. Ziglam, H. M., and R. G. Finch. 2002. Penicillin-resistant pneumococci: implications for management of community-acquired pneumonia and meningitis. Int. J. Infect. Dis. 6(Suppl. 1):S14-S20.

---

Antimicrobial Agents and Chemotherapy, January 2004, p. 53-62, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.53-62.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Jones, R. N., Fritsche, T. R., Ge, Y., Kaniga, K., Sader, H. S. (2005). Evaluation of PPI-0903M (T91825), a novel cephalosporin: bactericidal activity, effects of modifying in vitro testing parameters and optimization of disc diffusion tests. J Antimicrob Chemother 56: 1047-1052 [Abstract] [Full Text]  
• Sader, H. S., Fritsche, T. R., Kaniga, K., Ge, Y., Jones, R. N. (2005). Antimicrobial Activity and Spectrum of PPI-0903M (T-91825), a Novel Cephalosporin, Tested against a Worldwide Collection of Clinical Strains. Antimicrob. Agents Chemother. 49: 3501-3512 [Abstract] [Full Text]  
• Vouillamoz, J., Entenza, J. M., Hohl, P., Moreillon, P. (2004). LB11058, a New Cephalosporin with High Penicillin-Binding Protein 2a Affinity and Activity in Experimental Endocarditis Due to Homogeneously Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 48: 4322-4327 [Abstract] [Full Text]  

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sader, H. S. Articles by Jones, R. N. Search for Related Content PubMed PubMed Citation Articles by Sader, H. S. Articles by Jones, R. N.