In vitro activity of tedizolid against Staphylococcus aureus and Streptococcus pneumoniae collected in 2013 and 2014 from sites in Latin American countries, Australia, New Zealand, and China.

Tedizolid is an oxazolidinone with an antimicrobial in vitro potency advantage against Gram-positive bacterial pathogens compared to other currently marketed drugs in this class, including linezolid. Tedizolid was compared to linezolid when tested against Staphylococcus aureus and Streptococcus pneumoniae isolates collected from countries in Latin America and the Asia-Pacific. Isolates were tested by broth microdilution susceptibility methods against tedizolid, linezolid, and non-class comparators in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. The activity of tedizolid against S. aureus was potent and consistent in Latin America (MIC90, 0.5 mg/L), Australia and New Zealand (MIC90, 0.25 mg/L), and China (MIC90, 0.5 mg/L). Based on MIC90 results, tedizolid was four- to eight-fold more active than linezolid against S. aureus, including both methicillin-susceptible and -resistant isolates. Only two tedizolid non-susceptible strains were observed; both had intermediate minimum inhibitory concentration (MIC) values of 1 mg/L, for which the MICs of linezolid was higher (≥2 mg/L). Tedizolid (MIC90, 0.25 mg/L) was four-fold more potent than linezolid (MIC90, 1 mg/L) against S. pneumoniae in all countries that provided isolates. The findings from this study support the global clinical development of tedizolid for Gram-positive infections.

Comparative in vitro activities of ceftaroline and ceftriaxone against bacterial pathogens associated with respiratory tract infections: results from the AWARE surveillance study.

OBJECTIVES: Ceftaroline fosamil is indicated for the treatment of community-acquired bacterial pneumonia and ceftriaxone has an indication for lower respiratory tract infections. This study was conducted to compare the relative in vitro activities of these two agents against bacterial species associated with community-associated respiratory tract infections. METHODS: In all, 13 005 isolates of Staphylococcus aureus, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae were collected in 2012-14 from 39 countries in the Asia-Pacific region, Europe, Latin America and Africa-Middle East from respiratory tract specimens. The identification was confirmed centrally by MALDI-TOF and broth microdilution susceptibility testing and interpretation was done according to CLSI guidelines. RESULTS: Ceftaroline was 16-fold more potent against MSSA (MIC90 0.25 versus 4 mg/L) than ceftriaxone and ≥16-fold more potent against MRSA (MIC90 2 versus >32 mg/L). Ceftaroline was 16-fold more potent against S. pneumoniae (MIC90 0.12-0.25 mg/L) compared with ceftriaxone (MIC90 1-2 mg/L), with higher MIC values observed among penicillin-non-susceptible isolates for both agents. Similar activity (MIC90 ≤0.03 mg/L) was observed for ceftaroline and ceftriaxone against H. influenzae, with higher MIC values observed in the Asia-Pacific region for both agents compared with other regions. Ceftaroline was 4- to 8-fold more active against M. catarrhalis (MIC90 0.12-0.25 mg/L) compared with ceftriaxone (MIC90 1 mg/L). CONCLUSIONS: These global MIC data demonstrated that ceftaroline exhibited superior in vitro activity compared with ceftriaxone against bacterial species that commonly cause community-associated respiratory tract infections.

In Vitro Activity of Gepotidacin, a Novel Triazaacenaphthylene Bacterial Topoisomerase Inhibitor, against a Broad Spectrum of Bacterial Pathogens.

Gepotidacin inhibits bacterial DNA replication through a mode different from that of fluoroquinolones. Gepotidacin and comparators were tested by broth and agar dilution against clinical isolates. The in vitro activities of gepotidacin were comparable against methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) isolates (MIC90, 0.5 µg/ml). The gepotidacin MIC90s were as follows (in micrograms per milliliter) for the indicated bacteria: Streptococcus pyogenes, 0.25; Escherichia coli, 2; Moraxella catarrhalis, ≤ 0.06; Streptococcus pneumoniae (0.25), Haemophilus influenzae, 1; Clostridium perfringens, 0.5; and Shigella spp., 1, including levofloxacin-resistant subsets. Gepotidacin warrants further investigation for clinical development.

Comparative in vitro activity of oral antimicrobial agents against Enterobacteriaceae from patients with community-acquired urinary tract infections in three European countries.

Enterobacteriaceae causing community-acquired urinary tract infections were examined in selected outpatient clinics and hospitals in Belgium, Germany and Spain using EUCAST breakpoints for susceptibility. A total of 1190 isolates were collected. Escherichia coli isolates were resistant to amoxicillin-clavulanic acid (28.1%), ciprofloxacin (23.4%) and trimethoprim-sulfamethoxazole (21.4%) compared with fosfomycin and nitrofurantoin (each, <1.5%). Ceftibuten (MIC50/90 0.25/0.5 mg/L) and ceftriaxone activity (MIC50/90 ≤0.25 mg/L) was comparable. Ceftibuten (MIC90 ≤0.25 mg/L) was also active against Proteus mirabilis and Klebsiella spp. Extended-spectrum ß-lactamase phenotypes were 7.1% for E. coli, 5.6% for Klebsiella pneumoniae and 0.4% for P. mirabilis. Resistance was common among men and elderly women.

Antimicrobial resistance and resistance mechanisms of Enterobacteriaceae in ICU and non-ICU wards in Europe and North America: SMART 2011-2013.

Intensive care units (ICUs) are often described as hotbeds of antimicrobial resistance, with high rates of extended-spectrum ß-lactamase (ESBL)-producing and multidrug-resistant (MDR) Enterobacteriaceae. Data from the SMART study were used to examine differences between the susceptibility of Enterobacteriaceae from ICU and non-ICU wards in Europe and North America. In total, 21,470 Enterobacteriaceae isolates from intra-abdominal and urinary tract infections were collected at 90 sites in 20 European and North American countries in 2011-2013. Susceptibility and ESBL phenotypes were determined using the CLSI broth microdilution method and breakpoints. Susceptibility was lower and ESBL and MDR rates were higher in ICUs, with much greater ICU/non-ICU differences in Europe than North America. Susceptibility was lower and ESBL and MDR rates were higher in Europe than in North America in both patient locations. Resistance among Enterobacteriaceae in Europe was largely driven by Klebsiella pneumoniae, which had high rates of ESBLs (41.2% in ICUs; mostly CTX-M) and carbapenemases (13.2%; mostly KPC and OXA). For all Enterobacteriaceae combined, only ertapenem and amikacin inhibited >90% of isolates in ICUs in both regions. In North America, ertapenem, imipenem and amikacin inhibited >90% of K. pneumoniae from ICUs, whereas in Europe only amikacin did. ESBL and MDR rates varied considerably within Europe. Antimicrobial resistance was higher in Europe than North America, especially in ICUs. Further surveillance at the country, hospital and even patient ward level, and investigation of reasons for these findings, would be useful for the development of effective strategies to reduce antimicrobial resistance in ICUs.

Dissemination of NDM metallo-ß-lactamase genes among clinical isolates of Enterobacteriaceae collected during the SMART global surveillance study from 2008 to 2012.

The prevalence of carbapenemase enzymes continues to increase. Among the Ambler class B enzymes is the New Delhi metallo-ß-lactamase (NDM). This particular enzyme is capable of hydrolyzing nearly all ß-lactam antimicrobial agents and has spread rapidly, becoming a global problem. Therapeutic treatment options for patients infected with isolates which produce this enzyme are difficult to manage, as cross-resistance to other antimicrobial classes is common. The Study for Monitoring Antimicrobial Resistance Trends (SMART) is a global surveillance study evaluating the antimicrobial susceptibilities of numerous Gram-negative bacterial species recovered from people with intra-abdominal and urinary tract infections. The Clinical and Laboratory Standards Institute methods and a molecular analysis identified 134 isolates of Enterobacteriaceae (nine species) and one Acinetobacter sp. with blaNDM genes. These isolates were collected in nine countries, and >95% of the isolates possessed the NDM-1 variant. The MIC90 values were >4 mg/liter and >8 mg/liter for ertapenem and imipenem, respectively. No tested ß-lactam or ß-lactamase inhibitor combination had activity against these isolates. Resistance to amikacin (79.9%) and levofloxacin (82.8%) was common. Nearly all the isolates encoded additional enzymes, including AmpC cephalosporinases and extended-spectrum ß-lactamases. There is an urgent need for infection control and continued global monitoring of isolates which harbor the NDM enzyme, as evidenced by recent outbreaks.

In vitro activity of tigecycline against isolates collected from complicated skin and skin structure infections and intra-abdominal infections in Africa and Middle East countries: TEST 2007-2012.

Complicated skin and skin structure infections (cSSSIs) and intra-abdominal infections (IAIs) are problematic due to decreasing therapeutic options available against multidrug-resistant pathogens common among these types of infections. A total of 2245 isolates from African and the Middle Eastern (AfME) countries were collected to determine in vitro activity for tigecycline and comparators during 2007-2012 as part of the Tigecycline Evaluation Surveillance Trial program. Tigecycline was launched in the AfME in 2007 and remains active against a wide range of targeted pathogens worldwide. Isolates were recovered from cSSSI (1990) and IAI (255) from 38 sites in 11 AfME countries. Staphylococcus aureus was the most common species from cSSSI (27.9%), and the methicillin-resistant S. aureus rate was 25%. Enterococcus spp. (7.1%) and Streptococcus agalactiae (2.9%) were other common Gram-positive pathogens represented. Enterobacter spp. (14.5%), Pseudomonas aeruginosa (13.9%), Escherichia coli (11.4%), Klebsiella spp. (10.9%), and Acinetobacter spp. (7.2 %) were the most common Gram-negative species collected. Tigecycline MIC(90) values were 0.25 µg/mL against S. aureus. E. coli and Enterobacter spp. had tigecycline MIC(90) values of 1 and 2 µg/mL, respectively. E. coli was the most frequently collected species from IAI (28.3%), followed by Klebsiella spp. (20.8%), Enterococcus spp. (11.8%), and Stenotrophomonas maltophilia (6.3%). Isolates collected from IAI had the following tigecycline MIC(90) values: E. coli (1 µg/mL), Klebsiella spp. and other Enterobacteriaceae (2 µg/mL), Enterococcus spp. (0.25 µg/mL), and S. maltophilia (1 µg/mL). Tigecycline in vitro activity was observed against a broad spectrum of bacterial species, including strains resistant to other antimicrobial classes.

In vitro activity of tigecycline and comparators against carbapenem-resistant Enterobacteriaceae in Africa-Middle East countries: TEST 2007-2012.

Multidrug-resistant (MDR) Enterobacteriaceae are an emerging concern for healthcare providers. Infections caused by MDR pathogens are associated with increased costs, length of hospital stay, and morbidity and mortality rates. Carbapenem-resistant Enterobacteriaceae (CRE) continue to increase, and infections with these organisms are observed worldwide not only as hospital-acquired infections but also as community-acquired infections. Increasing antimicrobial resistance dictates the need for continued surveillance studies of common and MDR pathogens. The Tigecycline Evaluation Surveillance Trial (TEST) examined the susceptibility of pathogens isolated in Africa and the Middle East from 2007 to 2012. A total of 4155 Enterobacteriaceae isolates were evaluated to determine the in vitro activity and changes in resistance patterns for tigecycline and comparators. Carbapenem resistance was found in 191 (4.6%) of the isolates tested. Klebsiella pneumoniae was the most common CRE (64.9%), followed by Enterobacter cloacae (14.1%) and Escherichia coli (9.9%). Tigecycline MIC90 values (minimum inhibitory concentration required to inhibit 90% of the isolates) were 2µg/mL against all of these enteric species, with susceptibility rates of 96.8%, 92.6% and 100%, respectively. Tigecycline had in vitro activity against CRE, with a 95.3% susceptibility rate.

Update of the activity of cefditoren and comparator oral beta-lactam agents tested against community-acquired Streptococcus pneumoniae isolates (USA, 2004-2006).

Cefditoren and other orally administered cephalosporins are infrequently included in resistance surveillance studies. Here we evaluated 359 contemporary (2004-2006) strains of Streptococcus pneumoniae, including penicillin-intermediate (12.0%) and -resistant (22.8%) subsets from United States patients by reference broth microdilution methods. Cefditoren was the most potent cephalosporin tested (MIC(50), 0.015 mg/L), including against penicillin-intermediate strains (MIC(50), 0.12 mg/L), and was two-, four- and eight-fold more active than cefuroxime, cefdinir and cefprozil, respectively. Penicillin-resistant strains were largely resistant to all tested ss-lactams. We confirm the continued spectrum and potency for cefditoren against S. pneumoniae that surpasses that of other orally administered cephalosporins.

Comparisons of the in vitro susceptibility testing results for garenoxacin using six different national methods: report from the garenoxacin international bridging study.

BACKGROUND: Laboratories worldwide carry out MIC/disc diffusion (DD) tests using various national methods, often published by local organizations. Potentially different results may complicate drug development or registration between the US methods and those used in the European Union (EU). This study uses a new des-F(6)quinolone, garenoxacin, to compare in vitro results among the most utilized antimicrobial susceptibility testing methods. METHODS: Investigators in France, Germany, Spain, Sweden and the UK tested two bacterial collections designated, challenge (CC; n = 330) containing quinolone-resistant strains and national (NC; n = 540) that were recent clinical isolates (2000-2001). Results were compared with values derived from the National Committee for Clinical Laboratory Standards (NCCLS) methods, carried out by the US coordinating site. Discords (greater than four-fold) between MIC method results were repeated. Results were analysed for variation from the NCCLS results (+/-1-2 dilutions or greater than 3-6 mm) and by regression statistics. Ciprofloxacin was used as the control quinolone agent. RESULTS: CC and NC testing compliance averaged 98.4% and 86.4% among participating centres, respectively, and correlation (r) of the national method to the NCCLS MIC was: France (0.98), Germany (0.95), Spain (0.98), Sweden (0.96) and UK (0.95). CC produced MIC results that were identical to the NCCLS (Spain) to 0.6 x log(2) greater (Germany), but the percentage of strains +/-2 dilutions versus NCCLS MIC results was 98% (Germany)-100% (Sweden, UK). Similar patterns were observed for the NC (r = 0.93-0.98), and all nations had >99% of results within +/-2 dilutions (+/-6 mm for disc tests) of NCCLS values. MIC results from four national methods were slightly elevated compared to the NCCLS result (average 0.2 x log(2)). Control ciprofloxacin MIC and DD test results showed similar patterns. CONCLUSIONS: Inter-method garenoxacin susceptibility test results indicate that MIC and zone diameter endpoints derived from five EU methods compare favourably to the NCCLS method results, and generally were identical or a fraction of a log(2) dilution step higher. In contrast, zone diameters for garenoxacin and ciprofloxacin were routinely larger for the EU methods. This unique inter-method 'bridging' experiment allows regulatory agencies to better correlate in vitro testing results derived from procedures that use different national methodologies.

Revision of linezolid disk diffusion quality control guidelines for testing Staphylococcus aureus ATCC 25923: an independent seven-laboratory trial.

The accuracy of the published disk diffusion quality control (QC) range for linezolid for Staphylococcus aureus ATCC 25923 has been reported to be problematic, prompting a multicenter study to determine if revision was necessary. Five out of seven laboratories reported values outside the current QC range. Three participants had significant (13.3-60.0%) 'unacceptable' results with zones smaller than the established range. Overall, a range of 21-32 mm was shown (82.4% within the NCCLS published range). A revision (25-31 mm; 95.7% of results) of the QC range is necessary when testing S. aureus ATCC 25923 against linezolid.

Susceptibility trends of haemophilus influenzae and Moraxella catarrhalis against orally administered antimicrobial agents: five-year report from the SENTRY Antimicrobial Surveillance Program.

The assessment of orally administered antimicrobial susceptibilities of common pathogens that cause community-acquired respiratory tract infections (CARTI) has become exceedingly important due to the number of office visits for this indication. Numerous local, regional and global studies have documented the susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, the most common CARTI pathogens. SENTRY Antimicrobial Surveillance Program sites in North and Latin America, and Europe were requested to send a combined total of 100 isolates of these pathogens to the local monitor for reference broth microdilution testing (1997-2001). This study compared the susceptibility profiles of H. influenzae and M. catarrhalis isolates (13,370 strains) from the three geographic regions over a five year period. beta-lactamase mediated ampicillin resistance among H. influenzae was highest among North American isolates (27.9%) compared to Latin America and Europe (16.2 to 16.3%), although it was noted that during the five year study period, ampicillin resistance was steadily increasing in the latter two regions. Cefprozil (84.3% susceptible) and clarithromycin (81.1% susceptible) were also less active against North American H. influenzae isolates. Latin American isolates were much less susceptible to trimethoprim/sulfamethoxazole (T/S; 59.3%) compared to the other regions (75.8 to 78.6%). M. catarrhalis isolates were also significantly less susceptible to T/S in Latin America (10.5% resistance). The production of beta-lactamase enzymes among the M. catarrhalis isolates exceeded >95% in all three regions during the five year period. The fluoroquinolones (FQ) remained very active against these two respiratory pathogens with rare isolates with elevated FQ MIC results. It is apparent from this investigation that many commonly prescribed empiric treatments remain viable therapeutic options for CARTI caused by these two Gram-negative respiratory tract pathogens.

Validation of commercial dry-form broth microdilution panels for susceptibility testing of AZD2563, a new long-acting oxazolidinone.

The MIC results using a dry-form broth microdilution panel (TREK Diagnostic/Sensititre, Westlake, OH, USA) were validated for AZD2563, a novel oxazolidinone compound. In comparision studies against reference frozen-form panels, the commercial MIC results were the same as the reference calue for 82.7% of organisms and all results were within +/- one log2 dilution. Using 462 organisms, most from three genus groups (enterococci, staphylococci, streptococci), test results indicate that Sensititre MIC values were comparable to the reference test and can be utilized in clinical trials of for routine laboratory use when testing AZD2563 and linezolid, the drug class comparator.

Re-evaluation of quality control guidelines for gatifloxacin and garenoxacin (BMS284756) when susceptibility testing Haemophilus influenzae and Streptococcus pneumoniae.

An eight laboratory M23-A2 quality control (QC) study was performed for the re-evaluation of gatifloxacin, a new fluoroquinolone, using disk diffusion tests against Streptococcus pneumoniae ATCC 49619. The study also re-evaluated garenoxacin, a novel investigational des-F(6)-quinolone, using disk diffusion tests against S. pneumoniae ATCC 49619 and broth MIC for Hemophilus influenzae ATCC 49247. The gatifloxacin zone diameter results for S. pneumoniae did not indicate a need for QC range modification (26-34 mm; 98.3% of results); however, the garenoxacin zone diameters did demonstrate a need for a minor modification (1 mm; 26-34 mm; 96.3% of reported results). The broth MIC results for H. influenzae showed that 83.1% of the results were at the upper limit of the current range (0.008 microg/ml) published by the National Committee for Clinical Laboratory Standards (NCCLS). The proposed correction could either be 0.002-0.015 microg/mlor 0.004-0.015 microg/ml, each encompassing 100.0% of reported results (prior and current studies). All MIC results for control drugs, levofloxacin and moxifloxacin (disks) or gatifloxacin and clarithromycin (MIC), were within published NCCLS ranges.

Molecular epidemiology of extended-spectrum beta-lactamase-producing, fluoroquinolone-resistant isolates of Klebsiella pneumoniae in Taiwan.

Strains of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) have emerged worldwide. Concomitant ciprofloxacin resistance with ESBL production in K. pneumoniae isolates would severely restrict treatment options. Among 39 (18.5%) of 211 ESBL-KP isolates resistant to ciprofloxacin (MIC, >/=4 micro g/ml), 37 (95%) were high level resistant (MIC, >/=16 micro g/ml). These isolates were also cross resistant to the newer fluoroquinolones, including levofloxacin, gatifloxacin, gemifloxacin, and garenoxacin (BMS 284756). Sitafloxacin was most active against these ciprofloxacin-resistant ESBL-KP isolates with MICs for 67% of the isolates being

Comparative antimicrobial spectrum and activity of the desfluoroquinolone BMS284756 (T-3811) tested against non-fermentative Gram-negative bacilli.

OBJECTIVE: To compare the in vitro activity of BMS284756, a desfluoroquinolone, with four fluoroquinolones against 129 Pseudomonas aeruginosa strains, 97 Stenotrophomonas/Burkholderia group strains and 43 Acinetobacter spp. strains by three in vitro test methods. METHODS: The activity of BMS284756 was determined using the NCCLS reference broth microdilution method and E test (AB Biodisk, Solna, Sweden). These methods were compared for test accuracy, and 5-microg disk zone diameters were compared for interpretative accuracy using the susceptible breakpoint of < or =4 mg/L recommended by the manufacturer. All strains tested were derived from the 1999-2000 SENTRY Antimicrobial Surveillance Program organism collection. RESULTS: Comparative quinolone potency against P. aeruginosa was as follows: ciprofloxacin (MIC50, 0.25 mg/L) > gemifloxacin (MIC50, 0.5 mg/L) > levofloxacin = gatifloxacin (MIC50, 1 mg/L) > BMS284756 (MIC50, 4 mg/L). The MIC50 value for BMS284756 versus Stenotrophomonas/Burkholderia group was 2 mg/L. This potency was similar to that of other quinolones reported previously. The MIC50 results for the Acinetobacter spp. were ciprofloxacin at >2 mg/L, levofloxacin, gatifloxacin and gemifloxacin at 4 mg/L, and BMS284756 at >4 mg/L, all intermediate or resistant concentrations. The E test results compared favorably with the reference dilution test results for P. aeruginosa, Stenotrophomonas/Burkholderia group, and Acinetobacter spp., with an overall essential agreement of 97.0% +/- 2 log2 dilution steps. E test MIC results tended to be slightly lower when testing Stenotrophomonas/Burkholderia group strains. The disk diffusion method correlated well for P. aeruginosa (r = 0.94), Stenotrophomonas/Burkholderia group (r = 0.84) and Acinetobacter spp. (r = 0.99) strains. CONCLUSIONS: BMS284756 was generally less active than other comparison quinolones when tested against non-fermentative Gram-negative bacilli. Its spectrum remains equivalent only if dosing schedules substantiate a proposed susceptible breakpoint of < or =4 mg/L.

Multicentre assessment of linezolid antimicrobial activity and spectrum in Europe: report from the Zyvox antimicrobial potency study (ZAPS-Europe).

OBJECTIVE: To evaluate the in vitro spectrum and activity of linezolid, a recent oxazolidinone, according to well-controlled surveillance data from 42 medical centers in 13 countries throughout Europe. METHODS: Participants tested the susceptibility of 125 clinical strains of enterococcal and staphylococcal species against 13 drugs using reference broth microdilution trays or the standardized disk diffusion method of the National Committee for Clinical Laboratory Standards (NCCLS). Streptococcal species (n = 25 at each center) were tested against six drugs using E test (AB BIODISK, Solna, Sweden). Quality assurance testing was conducted using NCCLS-recommended strains and verification of resistance to linezolid and other selected agents was performed by retesting strains at the regional (Europe) and international (USA) monitor sites. RESULTS: A total of 5598 strains from throughout Europe (91% compliance) were tested. Vancomycin resistance was reported in only 0.6 and 3.0% of Enterococcus faecalis and E. faecium, respectively. Penicillin resistance occurred in 25.1% of Streptococcus pneumoniae; 4.9% at the high-level (> or =2 mg/L). The MIC90 for linezolid was 1 mg/L for streptococci and 2 mg/L for enterococci and staphylococci. Using the US FDA- and EUCAST-recommended susceptible breakpoints for linezolid, there were no confirmed reports of linezolid resistance [minimum inhibitory concentration (MIC), > or =8 mg/L]. The distribution of linezolid MIC values was unimodal and varied between 0.25 and 1 mg/L for streptococci (>90% of isolates), and between 1 and 2 mg/L for staphylococci (>90%) and enterococci (>95%). There were no differences in linezolid susceptibility in the vancomycin-, oxacillin-, or penicillin-resistant subsets of strains when compared to susceptible organism populations. CONCLUSIONS: Compared to the North American component of this study, there was substantially less vancomycin resistance among E. faecium isolates (Europe 3.0% vs. North America 63.4%). While the occurrence of penicillin-resistant S. pneumoniae in Europe and North America was similar (25.1% vs. 29.7%), the recovery of high-level penicillin-resistant strains was nearly three-fold higher in North America (4.9% vs. 13.2%). Only linezolid was universally active against all the tested Gram-positive isolates at

Antimicrobial susceptibility testing of clinical isolates of Bordetella pertussis from northern California: report from the SENTRY Antimicrobial Surveillance Program.

Reports of an increased clinical incidence of pertussis and the development of resistance by Bordetella pertussis to erythromycin prompted the collection and testing of recent clinical isolates from patients in northern California against a range of antimicrobial agents by the Etest (AB BIODISK, Solna, Sweden) method. All isolates were fully susceptible to all eight agents tested (MIC,

Antimicrobial activity of BMS 284756 (T-3811) against Neisseria gonorrhoeae tested by three methods.

The potency of BMS 284756, a novel des-F(6)-quinolone, was tested against 137 clinical isolates of Neisseria gonorrhoeae including 50 strains observed to be resistant to ciprofloxacin and other newer quinolones. The gonococci were tested using NCCLS methods (agar dilution, disk diffusion) and Etest. BMS 284756 potency versus N. gonorrhoeae was generally two- to four-fold greater than ciprofloxacin. Penicillin resistance in the absence of ciprofloxacin resistance did not affect BMS 284756 activity. However, elevated ciprofloxacin MICs were associated with higher BMS 284756 MIC results as follows (BMS 284756 MIC(50)/MIC range in mg/l): ciprofloxacin-susceptible strains (0.016 or 0.03/0.004-0.06), ciprofloxacin-intermediate strains (0.06 or 0.12/0.008-0.25) and ciprofloxacin-resistant strains (0.12 or 0.5/0.12-1). Etest MICs were routinely lower than those produced by the reference agar dilution method, but the correlation coefficient remained acceptable (r = 0.87). Similarly acceptable correlation was achieved with 5 microg disk zone diameters (r = 0.78), where all zones were > or = 28 mm (MIC < or = 1 mg/l). In conclusion, BMS 284756 was very active against N. gonorrhoeae (MIC(50) 0.03 mg/l overall) including ciprofloxacin-resistant strains and could be considered as a single-dose therapeutic option for gonorrhoea.