Superior in vitro activity of carbapenems over anti-methicillin-resistant Staphylococcus aureus (MRSA) and some related antimicrobial agents for community-acquired MRSA but not for hospital-acquired MRSA

Eighty-eight strains of Panton-Valentine leukocidin (PVL)-positive and -negative community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and 152 strains of hospital-acquired MRSA (HA-MRSA) were examined for susceptibility to carbapenems, oxacillin, and other antimicrobial agents. CA-MRSA strains were more susceptible to carbapenems (MIC₉₀, 1–4 μg/ml) than HA-MRSA strains (MIC₉₀, 32–64 μg/ml). Among the carbapenems examined, CA-MRSA strains were most susceptible to imipenem (MIC₅₀, 0.12 μg/ml; MIC₉₀, 1 μg/ml). A similar tendency was observed with oxacillin, but less markedly (MIC₉₀: 32 μg/ml for CA-MRSA and ≥256 μg/ml for HA-MRSA). This difference was also observed between CA-MRSA and HA-MRSA in susceptibility levels to cephems, erythromycin, clindamycin, and levofloxacin, but not to ampicillin, vancomycin, teicoplanin, linezolid, and arbekacin. The data indicate that, in terms of MIC₅₀ or MIC₉₀ values, CA-MRSA is 64–256 times more susceptible to imipenem than HA-MRSA, and for CA-MRSA, some carbapenems, e.g., imipenem, show better in vitro activity than anti-MRSA or some related agents.     

In vitro activity of twenty-three antimicrobials againstYersinia pestis strains

The microdilution method was used to determine the MICs of twenty-three antimicrobials against the 22 strains ofYersinia pestis that have been stocked in the National Institute of Health, Japan. The three fluoroquinolones, ofloxacin, ciprofloxacin and sparfloxacin, were most active, with MIC_90S of 0.125 μg/ml. The cephems showed considerable differences in activity: cefdinir and cefotaxime were the most active of this group, with MIC_90S of 0.25 μg/ml; they were followed by cefminox and latamoxef with MIC_90S of 0.5 μg/ml. The two carbapenems tested, imipenem and panipenem, were potently active at MIC_90S of 0.5 μg/ml. The study obtained MIC_90S for tetracycline and doxycycline ranging from 1.0 to 2.0 μg/ml, even though these drugs are known to be clinciall active against plague. Erythromycin and clarithromycin were the least active agents.     

Antimicrobial resistance and DNA-fingerprinting pattern of Burkholderia cepacia blood isolates

 The minimum inhibitory concentrations (MICs) of six antibiotics against 33 strains of Burkholderia cepacia isolated from 33 patients suspected of having sepsis or bacteremia were determined. All the B. cepacia isolates were resistant to gentamicin (MIC₉₀, >128 μg/ml), and 21.2% were resistant to imipenem (MIC₉₀, 16 μg/ml). They were susceptible to ciprofloxacin, ceftazidime, and minocycline (MIC₉₀, 2–8 μg/ml). The 33 blood isolates were classified into 12 types (A–L) by the pulsed-field gel electrophoresis pattern. All 11 of A type, 2/4 of B type, 3/4 of C type, 4/5 of E type, and both G type B. cepacia were isolated from different patients in the same hospital. These results suggest that B. cepacia can spread among patients with sepsis or bacteremia. Received: April 5, 2002 / Accepted: August 7, 2002     

Comparative antimicrobial activity of gatifloxacin tested against Campylobacter jejuni including fluoroquinolone-resistant clinical isolates

Campylobacter jejuni is an important pathogen that causes gastroenteritis, as well as other disease states such as meningitis and septic arthritis. In this study, the Etest (AB BIODISK, Solna, Sweden) results were compared to a reference agar dilution method using gatifloxacin, a new 8-methoxyfluoroquinolone. A total of 53 strains of C. jejuni initially isolated from patients in California and Mexico were tested. Results demonstrated a high correlation (r = 0.88) between the two utilized in vitro dilution methods. In addition, gatifloxacin activity was compared to that of ciprofloxacin, metronidazole, amoxicillin, erythromycin, chloramphenicol, gentamicin, tetracycline, and trimethoprim/sulfamethoxazole using the Etest. Gatifloxacin (MIC₉₀, 4μg/ml) was approximately eight- to 16-fold more potent than ciprofloxacin (Mic₉₀, > 32 μg/ml), a commonly used fluoroquinolone for Campylobacter infections. Eight strains highly resistant to ciprofloxacin (MIC₉₀, > 32 μg/ml) were tested for cross resistance against the newer fluoroquinolones (gatifloxacin, levofloxacin, trovafloxacin) and the rank order of potency was: gatifloxacin (MIC₅₀, 16 μg/ml) > trovafloxacin = levofloxacin (MIC₅₀, > 32 μg/mL). However, only 25% ciprofloxacin-resistant strains were inhibited by ≤ 1 μg/mL of gatifloxacin or trovafloxacin. These results for gatifloxacin against C. jejuni strains must be further assessed in the context of in vivo trials before the clinical role of this new fluoroquinolone can be determined. The Etest appears to be a simple and precise susceptibility test method for testing C. jejuni isolates against fluoroquinolones and other alternative therapeutic agents.     

Survey of antibiotic resistance in Pseudomonas aeruginosa by The Tokyo Johoku Association of Pseudomonas Studies

Pseudomonas aeruginosa resistance (minimum inhibitory concentration [MIC], ≥16 μg/ml defined as resistant) to meropenem, imipenem, panipenem, piperacillin, ceftazidime, cefozopran, cefoperazone, sulbactam/cefoperazone, amikacin, and tobramycin, as well as cross-resistance profiles, were investigated in P. aeruginosa strains isolated at eight hospitals in the Johoku area, Tokyo, during November 1998. Overall, 8.3% of isolates were imipenem-resistant and 4.6% were ceftazidime-resistant. However, the incidence of antibiotic-resistant P. aeruginosa was distinctly different at each hospital. P. aeruginosa resistance to imipenem ranged from (MIC) 1 to 64 μg/ml (MIC₉₀ 32 μg/ml), and its resistance to ceftazidime ranged from 2 to more than 128 μg/ml (MIC₉₀, 64 μg/ml). Meropenem (MIC range, ≤0.25 to 16 μg/ml) was more active than panipenem (MIC range, 2 to 64 μg/ml). Cefozopran was more active than piperacillin, cefoperazone, or sulbactam/cefoperazone, but many strains were resistant to cefoperazone (17/57). Our analysis found cross-resistance to many beta-lactams, but the degree of cross-resistance was very variable. Received: October 27, 2000 / Accepted: April 10, 2001     

Treatment of uncomplicated gonococcal urethritis by double-dosing of 200 mg cefixime at a 6-h interval

 The efficacy of antimicrobial regimens for the treatment of uncomplicated gonococcal urethritis depends partially upon the period of time (therapeutic time) during which the drug concentration in the blood after the concentration peak is greater than four times the minimum inhibitory concentration for 90% of clinical isolates of Neisseria gonorrhoeae (MIC₉₀). A therapeutic time of at least 10 h is suggested as an important determinant for elimination of 95% or more of the infection. In this study, therapeutic times for a single 400-mg dose of cefixime at various MIC₉₀s were calculated, and pharmacokinetic profiles of double-dosing of 200 mg cefixime at various intervals were simulated. Subsequently, a dosing interval of 6 h was tested in 6 healthy Japanese men, and then 93 Japanese men with gonococcal urethritis were treated with a regimen of two 200-mg doses of cefixime given at a 6-h interval. For a single dose of 400 mg cefixime, therapeutic times were calculated to be 12.8, 9.1, 5.4, and 1.7 h for MIC₉₀s of 0.06, 0.125, 0.25, and 0.5 μg/ml, respectively. In the simulation study of double-dosing of 200 mg cefixime at a 6-h interval, the therapeutic times for the MIC₉₀s of ≤0.125 μg/ml were longer than 10 h. Of the 93 patients, 68 were evaluated for microbiological outcome, and N. gonorrhoeae was eradicated in 60 (88.2%). The MIC₉₀ of cefixime for the 61 isolates tested was 0.125 μg/ml. All strains with MICs of ≤0.06 μg/ml were eradicated, whereas 8 of 16 strains with MICs of ≥0.125 μg/ml persisted after treatment. This regimen would not be effective against infection by strains exhibiting cefixime MIC₉₀s of ≥0.125 μg/ml. For such strains, a different regimen with a higher dose of cefixime would be required. Received: July 10, 2002 / Accepted: September 21, 2002 Acknowledgments We thank Kohji Ishibashi and Kohji Takeshita, at Fujisawa Pharmaceutical Co., Ltd., for pharmacokinetic analyses.     

In Vitro Activities of Six New Fluoroquinolones against Brucella melitensis

We have tested the in vitro activities of eight fluoroquinolones against 160 Brucella melitensis strains. The most active was sitafloxacin (MIC at which 90% of the isolates are inhibited [MIC₉₀], 0.12 μg/ml). In decreasing order, the activities (MIC₉₀s) of the rest of the tested fluoroquinolones were as follows: levofloxacin, 0.5 μg/ml; ciprofloxacin, trovafloxacin, and moxifloxacin, 1 μg/ml; and ofloxacin, grepafloxacin, and gatifloxacin, 2 μg/ml.     

In Vitro Activity of Ceftaroline-Avibactam against Gram-Negative and Gram-Positive Pathogens Isolated from Patients in Canadian Hospitals from 2010 to 2012: Results from the CANWARD Surveillance Study

The in vitro activities of ceftaroline-avibactam, ceftaroline, and comparative agents were determined for a collection of bacterial pathogens frequently isolated from patients seeking care at 15 Canadian hospitals from January 2010 to December 2012. In total, 9,758 isolates were tested by using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method (document M07-A9, 2012), with MICs interpreted by using CLSI breakpoints (document M100-S23, 2013). Ceftaroline-avibactam demonstrated potent activity (MIC₉₀, ≤0.5 μg/ml) against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Morganella morganii, Citrobacter freundii, and Haemophilus influenzae; >99% of isolates of E. coli, K. pneumoniae, K. oxytoca, P. mirabilis, M. morganii, C. freundii, and H. influenzae were susceptible to ceftaroline-avibactam according to CLSI MIC interpretative criteria for ceftaroline. Ceftaroline was less active than ceftaroline-avibactam against all species of Enterobacteriaceae tested, with rates of susceptibility ranging from 93.9% (P. mirabilis) to 54.0% (S. marcescens). All isolates of methicillin-susceptible Staphylococcus aureus (MIC₉₀, 0.25 μg/ml) and 99.6% of methicillin-resistant S. aureus isolates (MIC₉₀, 1 μg/ml) were susceptible to ceftaroline; the addition of avibactam to ceftaroline did not alter its activity against staphylococci or streptococci. All isolates of Streptococcus pneumoniae (MIC₉₀, 0.03 μg/ml), Streptococcus pyogenes (MIC₉₀, ≤0.03 μg/ml), and Streptococcus agalactiae (MIC₉₀, 0.015 μg/ml) tested were susceptible to ceftaroline. We conclude that combining avibactam with ceftaroline expanded its spectrum of activity to include most isolates of Enterobacteriaceae resistant to third-generation cephalosporins, including extended-spectrum β-lactamase (ESBL)- and AmpC-producing E. coli and ESBL-producing K. pneumoniae, while maintaining potent activity against staphylococci and streptococci.     

Daptomycin Activity against Uncommonly Isolated Streptococcal and Other Gram-Positive Species Groups

A total of 1,356 clinical isolates were tested against daptomycin by broth microdilution methods. Daptomycin was active against seven groups of viridans group streptococci (MIC₅₀ and MIC₉₀ values ranging from ≤0.06 and ≤0.06 μg/ml [Streptococcus bovis and Streptococcus dysgalactiae] to 0.5 and 1 μg/ml [Streptococcus mitis, Streptococcus oralis, and Streptococcus parasanguinis], respectively), beta-hemolytic streptococci serogroups C, F, and G (MIC₅₀ and MIC₉₀, ≤0.06 to 0.25 and 0.12 to 0.25 μg/ml, respectively), Corynebacterium spp. (MIC₅₀ and MIC₉₀, ≤0.06 and 0.12 μg/ml, respectively), and Micrococcus spp. (MIC₅₀ and MIC₉₀, ≤0.06 and 0.25 μg/ml, respectively). Listeria monocytogenes exhibited higher daptomycin MICs (MIC₅₀ and MIC₉₀, 2 and 4 μg/ml, respectively) than other tested organisms.     

Epidemiological survey of rifampicin resistance in clinic isolates of Brucella melitensis obtained from all regions of Turkey

The aim of the present study was to assess the antimicrobial susceptibility of Brucella melitensis isolates to rifampicin (RIF) depending on time and regional differences. A total of 94 human Brucella isolates collected in an 8-year period from the beginning of 2002 to the end of 2009 throughout Turkey were investigated. The isolates were identified at species and biovar levels by conventional methods, and minimum inhibitory concentrations (MIC) of RIF was determined by using the E test method. All isolates were identified as B. melitensis (93 isolates, biovar 3; 1, biovar 1), and MIC₅₀ and MIC₉₀ values of RIF were 1 and 1.5 μg/ml, respectively (MIC range, 0.25–1.5 μg/ml). All isolates were sensitive to RIF except 2 isolates, which had intermediate susceptibility to RIF. These findings indicated that B. melitensis biovar 3 may be the most frequently agent responsible for human brucellosis in Turkey. None of the isolates in our region was resistant to RIF.     

Antimicrobial Activity of Ceftolozane-Tazobactam Tested against Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns Isolated in U.S. Hospitals (2011-2012)

Ceftolozane/tazobactam, a novel antimicrobial agent with activity against Pseudomonas aeruginosa (including drug-resistant strains) and other common Gram-negative pathogens (including most extended-spectrum-β-lactamase [ESBL]-producing Enterobacteriaceae strains), and comparator agents were susceptibility tested by a reference broth microdilution method against 7,071 Enterobacteriaceae and 1,971 P. aeruginosa isolates. Isolates were collected consecutively from patients in 32 medical centers across the United States during 2011 to 2012. Overall, 15.7% and 8.9% of P. aeruginosa isolates were classified as multidrug resistant (MDR) and extensively drug resistant (XDR), and 8.4% and 1.2% of Enterobacteriaceae were classified as MDR and XDR. No pandrug-resistant (PDR) Enterobacteriaceae isolates and only one PDR P. aeruginosa isolate were detected. Ceftolozane/tazobactam was the most potent (MIC_50/90, 0.5/2 μg/ml) agent tested against P. aeruginosa and demonstrated good activity against 310 MDR strains (MIC_50/90, 2/8 μg/ml) and 175 XDR strains (MIC_50/90, 4/16 μg/ml). Ceftolozane/tazobactam exhibited high overall activity (MIC_50/90, 0.25/1 μg/ml) against Enterobacteriaceae and retained activity (MIC_50/90, 4/>32 μg/ml) against many 601 MDR strains but not against the 86 XDR strains (MIC₅₀, >32 μg/ml). Ceftolozane/tazobactam was highly potent (MIC_50/90, 0.25/0.5 μg/ml) against 2,691 Escherichia coli isolates and retained good activity against most ESBL-phenotype E. coli isolates (MIC_50/90, 0.5/4 μg/ml), but activity was low against ESBL-phenotype Klebsiella pneumoniae isolates (MIC_50/90, 32/>32 μg/ml), explained by the high rate (39.8%) of meropenem coresistance observed in this species phenotype. In summary, ceftolozane/tazobactam demonstrated high potency and broad-spectrum activity against many contemporary Enterobacteriaceae and P. aeruginosa isolates collected in U.S. medical centers. Importantly, ceftolozane/tazobactam retained potency against many MDR and XDR strains.     

Potency and Spectrum of Activity of AN3365, a Novel Boron-Containing Protein Synthesis Inhibitor,Tested against Clinical Isolates of Enterobacteriaceae and Nonfermentative Gram-Negative Bacilli

AN3365 (MIC_50/90, 0.5/1 μg/ml) was active against Enterobacteriaceae, including a subset of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains (MIC_50/90, 1/2 μg/ml). AN3365 inhibited 98.0 and 92.2% of wild-type (MIC_50/90, 2/8 μg/ml) and carbapenem-resistant (MIC_50/90, 4/8 μg/ml) Pseudomonas aeruginosa strains, respectively, at ≤8 μg/ml. AN3365 also demonstrated activity against wild-type Acinetobacter baumannii (MIC_50/90, 2/8 μg/ml) and Stenotrophomonas maltophilia (MIC_50/90, 2/4 μg/ml), while it was less active against multidrug-resistant A. baumannii (MIC_50/90, 8/16 μg/ml) and Burkholderia cepacia (MIC_50/90, 8/32 μg/ml).     

Molecular Characterization of Carbapenem-Nonsusceptible Enterobacterial Isolates Collected during a Prospective Interregional Survey in France and Susceptibility to the Novel Ceftazidime-Avibactam and Aztreonam-Avibactam Combinations

An interregional surveillance program was conducted in the northwestern part of France to determine the prevalence of carbapenem-nonsusceptible Enterobacteriaceae (CNSE) isolates and their susceptibility to ceftazidime-avibactam and aztreonam-avibactam combinations. Nonduplicate CNSE clinical isolates were prospectively collected from six hospitals between June 2012 and November 2013. MICs of ceftazidime and aztreonam, alone or combined with a fixed concentration of avibactam (4 μg/ml), and those of carbapenems (comparator agents) were determined. MICs of ertapenem in combination with phenylalanine arginine-naphthylamide dihydrochloride (PAβN) were also determined to assess active efflux. Genes encoding carbapenemases, plasmid-mediated AmpC enzymes, extended-spectrum β-lactamases (ESBLs), and major outer membrane proteins (OMPs) were amplified and sequenced. OMPs were also extracted for SDS-PAGE analysis. Among the 139 CNSE isolates, mainly Enterobacter spp. and Klebsiella pneumoniae, 123 (88.4%) were ertapenem nonsusceptible, 12 (8.6%) exhibited reduced susceptibility to all carbapenems, and 4 Proteeae isolates (2.9%) were resistant to imipenem. Carbapenemase production was detected in only two isolates (producing OXA-48 and IMI-3). In contrast, OMP deficiency, in association with AmpCs and/or ESBLs (mainly CTX-M-9, SHV-12, and CTX-M-15), was largely identified among CNSE isolates. The ceftazidime-avibactam and aztreonam-avibactam combinations exhibited potent activity against CNSE isolates (MIC₅₀/MIC₉₀, 1/1 μg/ml and 0.5/0.5 μg/ml, respectively) compared to that of ceftazidime and aztreonam alone (MIC₅₀/MIC₉₀, 512/512 μg/ml and 128/512 μg/ml, respectively). This study reveals the in vitro activity of ceftazidime-avibactam and aztreonam-avibactam combinations against a large collection of porin-deficient enterobacterial isolates that are representative of the CNSE recovered in the northern part of France.     

Ceftazidime-Avibactam Activity Tested against Enterobacteriaceae Isolates from U.S. Hospitals (2011 to 2013) and Characterization of β-Lactamase-Producing Strains

Ceftazidime-avibactam (MIC_50/90, 0.12/0.25 μg/ml) inhibited 99.9% (20,698/20,709) of Enterobacteriaceae isolates at ≤8 μg/ml. This compound was active against resistant subsets, including ceftazidime-nonsusceptible Enterobacter cloacae (MIC_50/90, 0.25/0.5 μg/ml) and extended-spectrum β-lactamase (ESBL) phenotype isolates. An ESBL phenotype was noted among 12.4% (1,696/13,692 isolates from targeted species) of the isolates, including 776 Escherichia coli (12.0% for this species; MIC_50/90, 0.12/0.25 μg/ml), 721 Klebsiella pneumoniae (16.3%; MIC_50/90, 0.12/0.25 μg/ml), 119 Klebsiella oxytoca (10.3%; MIC_50/90, 0.06/0.25 μg/ml), and 80 Proteus mirabilis (4.9%; MIC_50/90, 0.06/0.12 μg/ml) isolates. The most common enzymes detected among ESBL phenotype isolates from 2013 (n = 743) screened using a microarray-based assay were CTX-M-15-like (n = 307), KPC (n = 120), SHV ESBLs (n = 118), and CTX-M-14-like (n = 110). KPC producers were highly resistant to comparators, and ceftazidime-avibactam (MIC_50/90, 0.5/2 μg/ml) and tigecycline (MIC_50/90, 0.5/1 μg/ml; 98.3% susceptible) were the most active agents against these strains. Meropenem (MIC_50/90, ≤0.06/≤0.06 μg/ml) and ceftazidime-avibactam (MIC_50/90, 0.12/0.25 μg/ml) were active against CTX-M-producing isolates. Other enzymes were also observed, and ceftazidime-avibactam displayed good activity against the isolates producing less common enzymes. Among 11 isolates displaying ceftazidime-avibactam MIC values of >8 μg/ml, three were K. pneumoniae strains producing metallo-β-lactamases (all ceftazidime-avibactam MICs, >32 μg/ml), with two NDM-1 producers and one K. pneumoniae strain carrying the bla_KPC-2 and bla_VIM-4 genes. Therapeutic options for isolates producing β-lactamases may be limited, and ceftazidime-avibactam, which displayed good activity against strains, including those producing KPC enzymes, merits further study in infections where such organisms occur.     

Susceptibility change to antibiotics of Staphylococcus aureus strains isolated from skin infections between July 1994 and November 2000

 We measured the in-vitro susceptibility of 833 Staphylococcus aureus strains, isolated from skin infections at our hospital between July 1994 and November 2000, to 13 antimicrobial agents (ampicillin, methicillin, cephalexin, cefaclor, cefpodoxime proxetil, gentamicin, erythromycin, clindamycin, minocycline, vancomycin, fusidic acid, ofloxacin, and nadifloxacin). The concentrations required to inhibit 50% of the strains (MIC₅₀) of all these antimicrobial agents was extremely stable and ranged at levels below 3.13 μg/ml, except for gentamicin; in contrast, the MIC₉₀ was not uniform. The MIC₉₀ of vancomycin, fusidic acid, and nadifloxacin was very low and stable. No strain was resistant to vancomycin. The incidence of MRSA was 10%–20%. Received: November 1, 2001 / Accepted: February 4, 2002     

In-vitro antibacterial activities of cefpiramide and other broad-spectrum antibiotics against 440 clinical isolates in China

The in-vitro antibacterial activity of cefpiramide was compared with those of 15 other broad-spectrum cephalosporins. A total of 440 clinical strains of bacteria, including 9 bacterial species, were isolated from our hospital in 1998. The minimum inhibitory concentrations (MICs) of cefpiramide and five other antibiotics were determined for each species, using the agar-dilution method. The MIC of cefpiramide for Escherichia coli and Klebsiella pneumoniae was higher than those of three other third-generation cephalosporins, (ie, cefoperazone, ceftazidime, and ceftriaxone). Fifty-one percent (26/51) of Enterobacter cloacae isolates were resistant to cefpiramide. Cefoperazone/sulbactam and cefepime had greater activity against E. cloacae (resistance, 3.9% and 19.6%, respectively) than cefpiramide. Cefpiramide was more active against Pseudomonas aeruginosa (resistance rates, 12%) than cefoperazone, ceftazidime, ceftriaxone, aztreonam, and cefepime. Cefpiramide-resistant P. aeruginosa strains were resistant to ceftazidime, but 27% of ceftazidime-resistant strains were susceptible to cefpiramide; 15.3% of cefpiramide-resistant S. maltophilia strains were also susceptible to ceftazidime, but 50% of ceftazidime-resistant strains were still susceptible to cefpiramide. Cefoperazone/sulbactam was the most active agent against Acinetobacter baumannii, showing a resistance rate of 2%. Ampicillin/sulbactam, ceftazidime, and cefpiramide were the second most active agents, and about 50% of the tested strains were susceptible to these three antibiotics. Cefpiramide had an activity comparable to that of all tested β-lactams against oxacillin-susceptible Staphylococcus aureus (MIC₉₀, 2 μg/ml). Against Streptococcus pneumoniae and Haemophilus influenzae, cefpiramide had good activity, with an MIC₉₀ concentration at which 90% of the strain was inhibited of 1 μg/ml and 0.5 μg/ml, respectively. These results indicated that cefpiramide was more active against glucose non-fermenting bacteria than against Enterobacteriaceae, and was very active against oxacillin-susceptible Staphylo-coccus aureus, S. pneumoniae, and H. influenzae. Thus, cefpiramide may be a good choice of drug for the treatment of patients with infections with glucose non-fermenting bacteria and community acquired infections. Received: July 30, 1999 / Accepted: January 24, 2000     

In Vitro Activity of Plazomicin against 5,015 Gram-Negative and Gram-Positive Clinical Isolates Obtained from Patients in Canadian Hospitals as Part of the CANWARD Study, 2011-2012

Plazomicin is a next-generation aminoglycoside that is not affected by most clinically relevant aminoglycoside-modifying enzymes. The in vitro activities of plazomicin and comparator antimicrobials were evaluated against a collection of 5,015 bacterial isolates obtained from patients in Canadian hospitals between January 2011 and October 2012. Susceptibility testing was performed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, with MICs interpreted according to CLSI breakpoints, when available. Plazomicin demonstrated potent in vitro activity against members of the family Enterobacteriaceae, with all species except Proteus mirabilis having an MIC₉₀ of ≤1 μg/ml. Plazomicin was active against aminoglycoside-nonsusceptible Escherichia coli, with MIC₅₀ and MIC₉₀ values identical to those for aminoglycoside-susceptible isolates. Furthermore, plazomicin demonstrated equivalent activities versus extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing E. coli and Klebsiella pneumoniae, with 90% of the isolates inhibited by an MIC of ≤1 μg/ml. The MIC₅₀ and MIC₉₀ values for plazomicin against Pseudomonas aeruginosa were 4 μg/ml and 16 μg/ml, respectively, compared with 4 μg/ml and 8 μg/ml, respectively, for amikacin. Plazomicin had an MIC₅₀ of 8 μg/ml and an MIC₉₀ of 32 μg/ml versus 64 multidrug-resistant P. aeruginosa isolates. Plazomicin was active against methicillin-susceptible and methicillin-resistant Staphylococcus aureus, with both having MIC₅₀ and MIC₉₀ values of 0.5 μg/ml and 1 μg/ml, respectively. In summary, plazomicin demonstrated potent in vitro activity against a diverse collection of Gram-negative bacilli and Gram-positive cocci obtained over a large geographic area. These data support further evaluation of plazomicin in the clinical setting.     

Comparative In Vitro Activities of SMT19969, a New Antimicrobial Agent,against Clostridium difficile and 350 Gram-Positive and Gram-Negative Aerobic and Anaerobic Intestinal Flora Isolates

The comparative in vitro activity of SMT19969, a novel, narrow-spectrum, nonabsorbable agent, was studied against 50 ribotype-defined Clostridium difficile strains, 174 Gram-positive and 136 Gram-negative intestinal anaerobes, and 40 Gram-positive aerobes. SMT19969 was one dilution more active against C. difficile isolates (MIC range, 0.125 to 0.5 μg/ml; MIC₉₀, 0.25 μg/ml), including ribotype 027 strains, than fidaxomicin (range, 0.06 to 1 μg/ml; MIC₉₀, 0.5 μg/ml) and two to six dilutions lower than either vancomycin or metronidazole. SMT19969 and fidaxomicin were generally less active against Gram-negative anaerobes, especially the Bacteroides fragilis group species, than vancomycin and metronidazole, suggesting that SMT19969 has a lesser impact on the normal intestinal microbiota that maintain colonization resistance. SMT19969 showed limited activity against other Gram-positive anaerobes, including Bifidobacteria species, Eggerthella lenta, Finegoldia magna, and Peptostreptococcus anaerobius, with MIC₉₀s of >512, >512, 64, and 64 μg/ml, respectively. Clostridium species showed various levels of susceptibility, with C. innocuum being susceptible (MIC₉₀, 1 μg/ml) and C. ramosum and C. perfringens being nonsusceptible (MIC₉₀, >512 μg/ml). Activity against Lactobacillus spp. (range, 0.06 to >512 μg/ml; MIC₉₀, >512 μg/ml) was comparable to that of fidaxomicin and varied by species and strain. Gram-positive aerobic cocci (Staphylococcus aureus, Enterococcus faecalis, E. faecium, and streptococci) showed high SMT19969 MIC₉₀ values (128 to >512 μg/ml).     

Dalbavancin Activity When Tested against Streptococcus pneumoniae Isolated in Medical Centers on Six Continents (2011 to 2014)

Dalbavancin, a novel lipoglycopeptide, was approved for use in 2014 by regulatory agencies in the United States and Europe for the treatment of skin and skin structure infections. The activity of dalbavancin was also widely assessed by determination of its activity against Streptococcus pneumoniae clinical isolates collected from patients on six continents monitored during two time intervals (2011 to 2013 and 2014). A total of 18,186 pneumococcal isolates were obtained from 49 nations and submitted to a monitoring laboratory as part of the SENTRY Antimicrobial Surveillance Program for reference susceptibility testing. The potency of dalbavancin against S. pneumoniae was consistent across the years that it was monitored, with the MIC₅₀ and MIC₉₀ being 0.015 and 0.03 μg/ml, respectively, and all isolates were inhibited by ≤0.12 μg/ml. The activity of dalbavancin was not adversely influenced by nonsusceptibility to β-lactams (ceftriaxone or penicillin), macrolides, clindamycin, fluoroquinolones, or tetracyclines or multidrug resistance (MDR). Regional variations in dalbavancin activity were not detected, but S. pneumoniae strains isolated in the Asia-Pacific region were more likely to be nonsusceptible to penicillin and ceftriaxone as well as to be MDR than strains isolated in North or South America and Europe. Direct comparisons of potency illustrated that dalbavancin (MIC₅₀ and MIC₉₀, 0.015 and 0.03 μg/ml, respectively) was 16-fold or more active than vancomycin (MIC₅₀, 0.25 μg/ml), linezolid (MIC₅₀, 1 μg/ml), levofloxacin (MIC₅₀, 1 μg/ml), ceftriaxone (MIC₉₀, 1 μg/ml), and penicillin (MIC₉₀, 2 μg/ml). In conclusion, dalbavancin had potent and consistent activity against this contemporary (2011 to 2014) collection of S. pneumoniae isolates.     

In vitro evaluation of the activity of β-lactams,new quinolones,and other antimicrobial agents againstStreptococcus pneumoniae

The in vitro activities of the β-lactam and quinolone antibiotics panipenem, cefpodoxime, cefdinir, cefditoren, faropenem, tosufloxacin, levofloxacin and grepafloxacin were compared with similar conventional antibiotics against penicillin-resistantStreptococcus pneumoniae (PRSP). Pneumococcal isolates collected from October 1994 to March 1995 (n=1283) consisted of penicillin-susceptibleS. pneumoniae (PSSP; 59.2%), penicillin-intermediately-resistantS. pneumoniae (PISP;11.2%), and PRSP (29.6%). The isolates were highly susceptible to panipenem, faropenem and cefditoren with MIC₉₀ values of 0.125 μg/mL, 0.5 μg/mL and 0.5 μg/mL, respectively. Correlation coefficients for the relationships between the MICs of these β-lactam agents and that of penicillin G ranged from γ=0.7652 to γ=0.8022. These new β-lactam agents produced excellent bactericidal responses at concentrations greater than their MICs for PSSP concomitant with appropriate cellular morphologic changes. However, the bactericidal action of these antibiotics against PRSP was less pronounced and fewer instances of cell lysis were observed. The MIC₉₀ of cefpodoxime was similar to that of cefaclor, whereas that of cefdinir was between those of faropenem and cefpodoxime. The MIC distribution of the new quinolone agents showed 1 peak, but the MIC₉₀ values of tosufloxacin and grepafloxacin were both 0.5 μg/mL and that of levofloxacin was 2.0 μg/mL. Only 1% of all isolates demonstrated cross-resistance to all quinolone agents.