In vitro antimicrobial activity of doripenem, a new carbapenem.

The doripenem MICs at which 90% of the tested strains were inhibited ranged from 0.03 to 1 microg/ml for 10 species of Enterobacteriaceae (n = 351), from 0.03 to 0.12 microg/ml for oxacillin-susceptible staphylococci (n = 119), from 4 to 32 microg/ml for oxacillin-resistant staphylococci (n = 64), from < or =0.008 to 0.06 microg/ml for penicillin-susceptible streptococci (n = 132), and from 1 to 4 microg/ml for penicillin-resistant streptococci (n = 51). Overall, doripenem demonstrated in vitro activity similar to that of meropenem against gram-negative pathogens and to that of imipenem against gram-positive pathogens.

Baseline study to determine in vitro activities of daptomycin against gram-positive pathogens isolated in the United States in 2000-2001.

The activity of daptomycin was assessed by using 6,973 gram-positive bacteria isolated at 50 United States hospitals in 2000 and 2001. Among the isolates of Streptococcus pneumoniae (n = 1,163) collected, the rate of penicillin resistance was 16.1%; rates of oxacillin resistance among Staphylococcus aureus isolates (n = 1,018) and vancomycin resistance among Enterococcus faecium isolates (n = 368) were 30.0 and 59.5%, respectively. Multidrug-resistant (MDR) phenotypes (isolates resistant to three or more different chemical classes of antimicrobial agents) accounted for 14.2% of S. pneumoniae isolates, 27.1% of S. aureus isolates, and 58.4% of E. faecium isolates. For all gram-positive species tested, MICs at which 90% of the isolates tested were inhibited (MIC(90)s) and MIC ranges for directed-spectrum agents (daptomycin, quinupristin-dalfopristin, and linezolid) were identical or highly similar for isolates susceptible or resistant to other agents or MDR. Daptomycin had a MIC(90) of 0.12 micro g/ml for both penicillin-susceptible and -resistant isolates of S. pneumoniae. Against oxacillin-resistant S. aureus daptomycin had a MIC(90) of 0.5 micro g/ml, and it had a MIC(90) of 4 micro g/ml against both vancomycin-susceptible and -resistant E. faecium. The MIC(90)s for daptomycin and other directed-spectrum agents were unaffected by the regional or anatomical origin of isolates or patient demographic parameters (patient age, gender, and inpatient or outpatient care). Our results confirm the gram-positive spectrum of activity of daptomycin and that its activity is independent of susceptibility or resistance to commonly prescribed and tested antimicrobial agents. This study may serve as a baseline to monitor future changes in the susceptibility of gram-positive species to daptomycin following its introduction into clinical use.

The activity of levofloxacin and other antimicrobials against clinical isolates of Streptococcus pneumoniae collected worldwide during 1999-2002.

Streptococcus pneumoniae is the most important causative bacterial pathogen in respiratory infections. Globally, increasing levels of resistant strains highlight the need for continued surveillance programs to guide antibiotic choice. The current study compared susceptibility results of 4,788 strains of S. pneumoniae collected during 2001-2002 to susceptibility results from 3,884 strains collected from the same hospitals during 1999-2000. Participant centers were dispersed throughout five regions. By region, the prevalence of penicillin-resistant S. pneumoniae and percentage change from the previous 1999-2000 study was Mexico (26.0%, 12.5%), Brazil (7.9%; 5.5%), Asia (China, Hong Kong, South Korea, Thailand) (44.1%; 0.8%), Europe (France, Germany, Italy, Spain, UK) (11.1%; -0.6%) and South Africa (7.9; -1.8%). Multidrug-resistant (MDR) strains of S. pneumoniae were most frequently isolated from Asia (36.3%) compared with approximately 5% in the other four regions. Increases in the incidence of MDR isolates in Mexico (13.5%), Brazil (1.7%) and Asia (6.1%) were reported with no increases in MDR in South Africa and Europe. Levofloxacin resistance was rarely associated with MDR phenotypes. Levofloxacin maintained an MIC(90) of 1 microg/ml against the isolates collected from all five regions with no change during the study periods, despite differences in levofloxacin resistance rates between regions or nations (0%-3.2%). The prevalence of levofloxacin resistance (MIC > or =8 microg/ml) increased only slightly over the study period in Europe (0.3%-0.7%) and in Asia (3.0-3.2%), but little or no change was seen in Mexico (3.8%-0%) or Brazil or South Africa, where no levofloxacin resistant isolates were detected in either study period.

The activity of levofloxacin and comparator agents against clinical isolates of Streptococcus pneumoniae collected worldwide during 1999 and 2000.

BACKGROUND: Increases in penicillin-resistant Streptococcus pneumoniae have been documented worldwide. METHODS: During 1999 and 2000, 5,015 S. pneumoniae isolates were collected from 13 countries on five continents and tested for antimicrobial susceptibility. RESULTS: Penicillin resistance rates were as follows: South Korea, 70.1%; Hong Kong, 50.3%; Thailand, 39.3%; France, 28.7%; Spain, 24.8%; Mexico, 18.1%; Ireland, 11.8%; South Africa, 11.1%; Italy, 9.4%; United Kingdom, 3.1%; Brazil, 2.9%; China, 2.3%, and Germany, 0.7%. Resistance to azithromycin, clarithromycin and trimethoprim-sulfamethoxazole was commonly associated with penicillin resistance. Levofloxacin-resistant isolates were detected in 8 of 13 countries: Germany (0.2%), France (0.4%), Thailand (0.5%), South Korea (0.9%), Mexico (1.5%), Spain (1.6%), China (3.3%) and Hong Kong (8.0%). Multidrug resistance (resistance to >/=3 antimicrobial classes) occurred in 626/5,015 isolates (12.5%). Levofloxacin was active against 96.0% (601/626) of the multidrug-resistant (MDR) isolates and 99.7% (4,374/4,389) of the non-MDR isolates. CONCLUSION: Although relatively high levels of levofloxacin resistance were detected in China and Hong Kong, overall, levofloxacin remained active against >99% of clinical isolates of S. pneumoniae despite their resistance to other agents. Continued surveillance of S. pneumoniae will track any changes in levofloxacin activity, should they occur.

Phenotypic and genotypic analysis of levofloxacin-resistant clinical isolates of Streptococcus pneumoniae collected in 13 countries during 1999-2000.

During 1999-2000, 5015 isolates were collected from 13 countries and tested against levofloxacin. Overall, levofloxacin resistance minimum inhibitory concentration (MIC>or =8 mg/l) was found in 40 isolates (0.8%). The highest resistance rates were in Hong Kong (8.0%), China (3.3%) and Spain (1.6%). Levofloxacin retained an MIC(90) of 1 mg/l in all countries. Pulsed-field gel electrophoresis analysis of resistant isolates demonstrated the presence of clones in countries where levofloxacin resistance exceeded 1%, suggesting that the elevated resistance rates could result from resistant clones within participating hospitals. DNA-sequence analysis of the quinolone-resistance-determining regions of gyrA, gyrB, parC and parE genes showed that the most common mutations were in GyrA (Ser81Phe), ParC (Ser79Phe, Lys137Asn) and ParE (Ile460Val), accounting for 40% of the isolates tested. Levofloxacin-resistant isolates were generally non-susceptible to other fluoroquinolones tested. Future studies to characterise resistant isolates by other molecular methods may ensure that the appropriate counter-measures can be taken to control the spread of resistant isolates.

In vitro activities of novel nonfluorinated quinolones PGE 9262932 and PGE 9509924 against clinical isolates of Staphylococcus aureus and Streptococcus pneumoniae with defined mutations in DNA gyrase and topoisomerase IV.

Two 8-methoxy nonfluorinated quinolones (NFQs), PGE 9262932 and PGE 9509924, were tested against contemporary clinical isolates of Staphylococcus aureus (n = 122) and Streptococcus pneumoniae (n = 69) with genetically defined quinolone resistance-determining regions (QRDRs). For S. aureus isolates with wild-type (WT) sequences at the QRDRs, the NFQs demonstrated activities 4- to 32-fold more potent (MICs at which 90% of isolates are inhibited [MIC(90)s], 0.03 microg/ml) than those of moxifloxacin (MIC(90), 0.12 microg/ml), gatifloxacin (MIC(90), 0.25 microg/ml), levofloxacin (MIC(90), 0.25 microg/ml), and ciprofloxacin (MIC(90), 1 microg/ml). Against S. pneumoniae isolates with WT sequences at gyrA and parC, the NFQs PGE 9262932 (MIC(90), 0.03 microg/ml) and PGE 9509924 (MIC(90), 0.12 microg/ml) were 8- to 64-fold and 2- to 16-fold more potent, respectively, than moxifloxacin (MIC(90), 0.25 microg/ml), gatifloxacin (MIC(90), 0.5 microg/ml), levofloxacin (MIC(90), 2 microg/ml), and ciprofloxacin (MIC(90), 2 microg/ml). The MICs of all agents were elevated for S. aureus isolates with alterations in GyrA (Glu88Lys or Ser84Leu) and GrlA (Ser80Phe) and S. pneumoniae isolates with alterations in GyrA (Ser81Phe or Ser81Tyr) and ParC (Ser79Phe or Lys137Asn). Fluoroquinolone MICs for S. aureus strains with double alterations in GyrA combined with double alterations in GrlA were > or =32 microg/ml, whereas the MICs of the NFQs for strains with these double alterations were 4 to 8 microg/ml. The PGE 9262932 and PGE 9509924 MICs for the S. pneumoniae isolates did not exceed 0.5 and 1 microg/ml, respectively, even for isolates with GyrA (Ser81Phe) and ParC (Ser79Phe) alterations, for which levofloxacin MICs were > 16 microg/ml. No difference in the frequency of selection of mutations (< 10(-8) at four times the MIC) in wild-type or first-step mutant isolates of S. aureus or S. pneumoniae was detected for the two NFQs. On the basis of their in vitro activities, these NFQ agents show potential for the treatment of infections caused by isolates resistant to currently available fluoroquinolones.

Antimicrobial surveillance of Haemophilus influenzae in the United States during 2000-2001 leads to detection of clonal dissemination of a beta-lactamase-negative and ampicillin-resistant strain.

A 2000-2001 U.S. Haemophilus influenzae surveillance study (n = 1,434) detected nine (0.6%) beta-lactamase-negative and ampicillin-resistant (BLNAR) isolates collected from two different hospitals. The MICs of ampicillin for all nine isolates were 4 microg/ml, with results being reproducible; and all nine isolates were susceptible to amoxicillin-clavulanate, cefuroxime, cefprozil, macrolides, and fluoroquinolones. Pulsed-field gel electrophoresis of genomic DNA following SmaI digestion demonstrated identical patterns for each of the nine isolates, suggesting intra- and interhospital dissemination of a BLNAR clone.

Antimicrobial susceptibilities of Streptococcus pyogenes isolated from respiratory and skin and soft tissue infections: United States LIBRA surveillance data from 1999.

This study evaluated current levels of antimicrobial resistance and associated demographic trends among clinical isolates of Streptococcus pyogenes in the United States as part of the LIBRA surveillance initiative. In 1999, 2,742 isolates of S. pyogenes (2,039 respiratory; 405 skin and soft tissue; 148 blood) were collected from 324 clinical laboratories and centrally tested for antimicrobial susceptibility by the broth microdilution method. All isolates were susceptible to penicillin (MIC(90,) < or = 0.06 microg/mL), ceftriaxone (MIC(90,) < or =0.03 microg/mL), vancomycin (MIC(90,) 0.5 microg/mL), levofloxacin (MIC(90,) 1 microg/mL), and moxifloxacin (MIC(90,) 0.25 microg/mL). Twenty-four (0.9%) azithromycin-intermediate (MIC, 1 microg/mL) and 170 (6.2%) azithromycin-resistant (MIC, > or = 2 microg/mL) isolates were identified. Regionally, azithromycin resistance varied by < 5%, ranging from 3.0% in New England to 7.7% in the Pacific region. Azithromycin resistance was significantly higher (P < 0.001) among patients aged 15-64 years (8.3%) than patients < or =14 years (4.3%). This study found higher rates of macrolide resistance among S. pyogenes than previously reported in the United States and suggests that macrolide resistance is common among respiratory isolates from both younger and older patients. Fluoroquinolones (moxifloxacin > levofloxacin) demonstrated potent in vitro activity against all isolates of S. pyogenes tested, including those from skin and soft tissue infections. Given the higher rates of macrolide resistance reported in other countries and the seriousness of invasive infections, continued antimicrobial surveillance of S. pyogenes in the United States would be prudent.