Comparative in vitro activity of ceftaroline and comparator agents against nosocomial Gram-negative and Gram-positive clinically significant bacterial isolates from patients in a teaching hospital in Kuwait

The objective was to test the in vitro activities of ceftaroline and comparator agents against clinical isolates of Gram-negative and Gram-positive bacteria. Isolates were identified with VITEK II. Susceptibility testing was with E test. A total of 1264 isolates were tested. Compared to other cephalosporins, ceftaroline demonstrated excellent in vitro activities (MIC₉₀, ≤0.5 mg/L) against Escherichia coli, Salmonella spp. and Haemophilus influenzae. When matched with the comparator cephalosporins, ceftaroline demonstrated the greatest activity against methicillin-susceptible Staphylococcus aureus (MSSA), with MIC₉₀ of 0.25 mg/L. Ceftaroline’s MIC₉₀s against both community-associated methicillin-resistant S. aureus (MRSA) and hospital-acquired MRSA were 0.5 and 1 mg/L, respectively. Major discrepancies were noted between E test and disc diffusion tests for ceftaroline only against 16 Gram-negative and 16 Gram-positive isolates. Ceftaroline demonstrated an excellent in vitro activity against the majority of clinically significant Gram-negative and Gram-positive isolates obtained from proven cases of bacterial infections.     

Activity of tedizolid against gram-positive clinical isolates causing infections in Europe and surrounding areas (2014–2015)

Activities of tedizolid and comparators were evaluated against gram-positive isolates responsible for skin and skin structure infections, pneumonia, and bloodstream infections. Non-duplicate gram-positive isolates (8011) were collected from 20 European countries/regions.

Tedizolid (0.12?mg/L) showed similar results of minimum inhibitory concentration required to inhibit the growth of 50% of organisms (MIC₅₀) regardless of pathogen/group or infection type, except for coagulase-negative staphylococci, Enterococcus faecalis, and viridans group streptococci (VGS), against which tedizolid had MIC₅₀ values of 0.06, 0.25, and 0.06?mg/L, respectively. Similar results of tedizolid MIC₅₀ and minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC₉₀) (MIC_50/90, 0.12/0.12?mg/L) were obtained against methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus. Tedizolid, linezolid, and daptomycin were active against enterococci. Tedizolid (MIC₉₀, 0.12–0.25?mg/L), ceftaroline (MIC₉₀, 0.12?mg/L), and vancomycin (MIC₉₀, 0.25–0.5?mg/L) had the lowest MIC₉₀ values against Streptococcus pneumoniae and VGS, whereas ceftaroline (MIC₉₀, ≤0.015?mg/L), penicillin (MIC₉₀, ≤0.06?mg/L), ceftriaxone (MIC₉₀, ≤0.06–0.12?mg/L), and tedizolid (MIC₉₀, 0.12?mg/L) were the most potent against β-haemolytic streptococci.

Tedizolid displayed potent activity against gram-positive isolates from Europe, regardless of infection type.     

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.     

Insights into cancer surveillance in Central and Eastern Europe,Israel and Turkey

The current cancer landscape within transitional economies in central and Eastern Europe and the Mediterranean area is not particularly optimistic. Current perceptions are often based on extrapolations from other countries and regions; and hence the authors collaborated with the South Eastern Europe Oncology Group (SEEROG) to collect information on cancer registration in Central and Eastern Europe, Israel and Turkey. Healthcare authorities and specialist oncology centres in 21 countries in the region were contacted for information on cancer registries in their countries. Based on this information, the authors believe that the recording and reporting of data on cancer in the region is at an acceptable level. The authors discuss and compare institution‐ and population‐based registries, and present opinions on elements of an ‘ideal registry’ based on the survey replies and comparisons with other registries. A comparison with the sources used for GLOBOCAN 2008 illustrates the need for consistent data to be communicated, published and utilised throughout the region and the oncology community. The authors conclude by considering the potential value of collaboration between health authorities across the region, as well as between the clinical and epidemiological communities, to ensure that cancer data are consistently collected, verified and made public.     

In vitro activity of ceftaroline and ceftobiprole against methicillin-resistant Staphylococcus aureus with decreased susceptibility to vancomycin isolated in paediatric patients

Minimal inhibitory concentrations (MIC, mg/l) of ceftaroline and ceftobiprole were evaluated over 70 methicillin-resistant Staphylococcus aureus (MRSA) strains with vancomycin MIC ≥1 isolated in a paediatric hospital. The proportion of non-wild-type strains (MIC?>?epidemiological cut off) was 18% for ceftobiprole and 64% for ceftaroline. Only 1.4% of strains was resistant to ceftobiprole, and none to ceftaroline. These results are worrisome, since show the presence of non-negligible proportions of MRSA strains with high MIC values for ceftaroline and ceftobiprole in a setting where both drugs were never used.     

In vitro activity of telithromycin, quinupristin/dalfopristin, linezolid and comparator antimicrobial agents against Staphylococcus aureus clinical isolates

We have studied the prevalence of the different macrolide, lincosamide, streptograminB (MLS(B)) phenotypes among clinical Staphylococcus aureus isolates erythromycin- and/or oxacillin-resistant; and also the activity of other antimicrobial agents including telithromycin, quinupristin/dalfopristin, linezolid, aminoglycosides, chloramphenicol and vancomycin. We found that 64.86% of S. aureus were oxacillin-resistant. While the most prevalent MLS(B) phenotype among methicillin-resistant S. aureus (MRSA) was constitutive MLS(B) (cMLS) (83%), among methicillin-susceptible S. aureus (MSSA) it was inducible MLS(B) (iMLS(B)) (90%). Kanamycin resistance was more frequent than resistance to other aminoglycosides, being 100% for MRSA. Telithromycin was only active against iMLS(B), MS and erythromycin-susceptible isolates, although resistance rates were found among iMLS(B) MSSA (2.78%). Quinupristin/dalfopristin showed greater activity, with resistance rates of 2.5% for MRSA and 1.53% for MSSA. Both vancomycin and linezolid were fully active against all the isolates tested, with the highest MIC value being 2 microg/ml and 4 microg/ml, respectively. Among MRSA strains, 81.67% displayed resistance to five or more antimicrobials. This multiresistance was more frequently found among cMLS(B) strains (96.38% MRSA resistant to 6-9 agents).     

Determining the prevalence of SCCmec polymorphism,virulence and antibiotic resistance genes among methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from selected hospitals in west of Iran

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important pathogens worldwide and compared to other staphylococcal species that are associated with higher mortality rate. A total of 500 Staphylococcus spp. was collected from selected hospitals in Ilam, Kermanshah, Khorram Abad and Hamadan cities and, via phenotypic and genotypic methods, was assessed to find MRSA. The presence or absence of prevalent antibiotic resistance genes and virulence genes was evaluated among MRSA isolates, using polymerase chain reaction (PCR) method, and then the SCCmec typing of these isolates was assayed by multiplex PCR. A total of 372 (74.4%) Stapylococcus spp. isolates were identified as S. aureus, among which 200 (53.8%) possessed the mecA gene and were distinguished as MRSA. All of MRSA isolates contained blaZ gene. The frequency of ermA and ermC genes among erythromycin-resistant MRSA isolates was 21.6% and 66.7%, respectively. The frequency of the virulence genes eta, hla and sea among MRSA isolates was 10%, 80.5% and 100%, respectively. SCCmec type IV accounted for 30.6% of the MRSA isolates and SCCmec type III, SCCmec type II and SCCmec type I accounted for 30%, 22% and 17.5% of the isolates, respectively. The antibiotic resistance genes and the virulence genes of blaZ, hla, sea, eta and ermC had high frequencies among the MRSA isolates. This study showed that the antibiotic resistance genes had higher frequencies among SCCmec types I and IV, which confirms the previous reports in this field.     

Antimicrobial spectrum and potency of dalbavancin tested against clinical isolates from Europe and North America (2003): initial results from an international surveillance protocol

Dalbavancin is a bactericidal dimethylaminopropyl amide glycopeptide derivative possessing an extended serum elimination half-life in humans that allows once-weekly dosing for the therapy of Gram-positive infections. Strains from this baseline surveillance protocol in North America (NA; USA and Canada) and Europe (EU, 14 countries) were sampled in 2003. A total of 7,765 Gram-positive isolates (3,695 from NA and 4,070 from EU) were tested by reference broth microdilution methods against dalbavancin and 10 comparator agents. Species were analyzed separately by resistance phenotypes such as methicillin- (oxacillin-) resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae. Dalbavancin and other glycopeptides were very active against staphylococci (n=4648) with dalbavancin being 16- to 32-fold more potent than vancomycin (MIC90, 0.06 versus 2 mg/L). MRSA rates were greater (31.6%) in NA than in EU (26.1%). Quinupristin/dalfopristin resistance (MIC, > or = 2 mg/L; 0.1-0.5%) was documented more often in EU compared to NA. Dalbavancin (MIC50, 0.03-0.06 mg/L) was active against enterococci, except VanA resistance phenotypes. VRE rates were lower in EU (8.3%) then in NA (35.9%) from this resistance-enhanced enterococcal collection. Streptococci (dalbavancin MIC90, 0.016-0.03 mg/L) were generally most susceptible to glycopeptides (100.0%), quinupristin/dalfopristin (98.6-100.0%) and linezolid (100.0%); but dalbavancin was 16-fold more active than comparators. All vancomycin-susceptible enterococci and > 90% of vanB VRE had dalbavancin MIC values at < or = 1 mg/L,but vanA VRE strains had dalbavancin MIC results ranging from 0.06 to > 8 mg/L (median MIC, > or = 8 mg/L). Dalbavancin MIC values were not adversely influenced by geographic region or resistance phenotype (except vanA VRE). Infrequently isolated Gram-positive organisms such as Bacillus spp. (MIC90, 0.12 mg/L), Corynebacterium spp. (MIC90, 0.12 mg/L), Listeria monocytogenes (MIC90, 0.25 mg/L) and Micrococcus spp. (MIC90, 0.03 mg/L) were very susceptible to dalbavancin. In conclusion, these 2003 baseline resistance surveillance findings confirm the potent dalbavancin activity compared to several comparator agents against important Gram-positive pathogens. This high volume international survey indicates potential therapeutic roles for dalbavancin against many troublesome resistant Gram-positive phenotypes.     

Antibiotic resistance patterns of Gram-negative and Gram-positive strains isolated from inpatients with nosocomial infections in a tertiary hospital in Beijing,China from 2011 to 2014

This study was to evaluate the resistance of antimicrobial agents against pathogens from inpatients with nosocomial infection collected in Beijing, China, during 2011–2014. Measurement of minimum inhibitory concentrations (MICs) was carried out using the broth microdilution method with the Clinical and Laboratory Standards Institute (CLSI) guidelines as the indicator. A total of 5442 Gram-negative and 806 Gram-positive isolates were collected in this study in 2011–2014. Two carbapenem-resistant strains appeared among Escherichia coli (E. coli), while imipenem-resistant isolates increased in proportion from 0% to 8.2% among Klebsiella pneumonia (K. pneumonia) during 4 year. Acinetobacter baumannii (A. baumannii) revealed severe antibacterial resistance to most antimicrobial agents. In contrast, a decreasing trend on resistance had been observed among Pseudomonas aeruginosa (P. aeruginosa) especially after 2012, range from 1.8% for co-trimoxazole to 13.5% for piperacillin. The resistance of Staphylococcus aureus (S. aureus) also had the lowest resistant to linezolid and vancomycin (0.1%). In summary, antimicrobial-resistant nosocomial pathogens have gradually increased from 2011 to 2014, so improved surveillance of hospital-acquired infections and effective infection-control measures may be the best way to solve the present problem.     

Activity of daptomycin and selected antimicrobial agents tested against Staphylococcus aureus from patients with bloodstream infections hospitalized in European medical centers

Daptomycin is a cyclic lipopeptide with potent bactericidal activity against Gram-positive organisms and has been approved by the United States Food and Drug Administration for the treatment of Staphylococcus aureus bacteremia and infectious endocarditis (right-side). We evaluated the activity of daptomycin against bloodstream infection S. aureus strains from 4,799 patients hospitalized in 32 medical centers (12 European countries, Turkey and Israel) with bloodstream infections (BSI) during a 5-year period (2002-2006). Intravenous catheters were the source of infection in 15% of cases, and those strains were analyzed separately. All strains were susceptibility tested by reference broth microdilution methods utilizing calcium supplementation (50 mg/L) when testing daptomycin. Bactericidal activity of daptomycin and vancomycin were evaluated against a subset of 50 randomly selected strains. Daptomycin (MIC(50/90), 0.25/0.5 mg/L), vancomycin (MIC (50/90), 1/1 mg/L), and linezolid (MIC(50/90), 2/2 mg/L), were highly active (>99.9% susceptibility) against the strains evaluated; and daptomycin was the most potent (lowest MIC(90) ) among these compounds. Resistance rates to oxacillin and levofloxacin were generally elevated, especially when an intravenous catheter was the source of infection.     

In vitro susceptibilities of cerebrospinal fluid isolates of Cryptococcus neoformans collected during a ten-year period against fluconazole,voriconazole and posaconazole (SCH56592)

We investigated the in vitro susceptibilities of 213 cerebrospinal fluid isolates of Cryptococcus neoformans isolated from 192 patients through a 10-year period, 1990-99, against fluconazole, voriconazole and posaconazole (SCH56592) by using the NCCLS (National Committee for Clinical Laboratory Standards) macrodilution method, M27-A. The overall MICs50 and MICs90 of fluconazole, voriconazole and posaconazole were found to be 2 and 8 micro g ml-1, 相似文献   

Antimicrobial activity of daptomycin tested against gram-positive strains collected in European hospitals: results from 7 years of resistance surveillance (2003-2009)

Daptomycin is a cyclic lipopeptide approved by the European medicines Agency (EMEA) for the treatment of complicated skin and soft tissue infections (cSSTI) and Staphylococcus aureus bacteremia and endocarditis. We evaluated the in vitro activity of daptomycin and comparators tested against clinical isolates from european hospitals over a 7-year period (2003-2009). A total of 36,769 consecutive isolates were collected in 34 medical centers located in 13 European countries, Turkey and Israel. the collection included S. aureus (18,352; 27.2% oxacillin-resistant [MRSA]); coagulase-negative staphylococci (CoNS; 6,874), Enterococcus spp. (7,241; 9.4% vancomycin-resistant), β-hemolytic (3,009), viridans group streptococci (1,176), and Streptococcus bovis/gallolyticus (107). The organisms were isolated mainly from patients with bloodstream infection (56%) or cSSTI (23%). Daptomycin was very active against S. aureus and CoNS (MIC(50/90), 0.25/0.5 mg/l for both organisms), and its activity was not adversely influenced by oxacillin resistance. All Enterococcus faecalis strains were susceptible to daptomycin (MIC(50/90), 1/1 mg/l). Daptomycin (MIC(50/90), 2/2 mg/l; 100.0% susceptible) and linezolid (MIC(50/90), 1/2 mg/l; 99.7% susceptible) were the most active agents tested against vancomycin-resistant E. faecium. Vancomycin- resistant and -susceptible enterococcal strains were equally susceptible to daptomycin. Daptomycin was also active against β-hemolytic streptococci (MIC(50/90), 0.06/0.25 mg/l; 100.0% susceptible), viridans group streptococci (MIC(50/90), 0.25/0.5 mg/l; 99.8% susceptible) and S. bovis (MIC(50/90), 0.06/0.12 mg/l; 100.0% susceptible).In summary, daptomycin was very potent against this large collection (36,769) of Gram-positive organisms isolated in european hospitals, and its activity remained stable across the 7-year period evaluated (2003-2009), using reference methods and interpretive criteria. Decreases in daptomycin potency were not observed since EMEA approval and widespread clinical use, and emerging resistance to other compounds did not adversely influence daptomycin activity against contemporary Gram-positive species.     

Activity of Plazomicin (ACHN-490) against MDR clinical isolates of Klebsiella pneumoniae,Escherichia coli,and Enterobacter spp. from Athens,Greece

Abstract

The in vitro activity of plazomicin was evaluated against 300 multidrug resistant (MDR) (carbapenemase and/or ESBL-producing) isolates from four hospitals in Athens, an area where carbapenemase-producing organisms are endemic. Most of the isolates were also resistant to the legacy aminoglycosides with the MIC₅₀/MIC₉₀ to tobramycin, amikacin and gentamicin being 32/>32, 32/>32 and 4/>8 μg/ml, respectively. ACHN-490 retained activity (MICs?4 μg/ml) against all isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. tested with MIC₅₀ and MIC₉₀ of 1 and 2 μg/ml, respectively, irrespective of their MDR phenotype and it represents a promising alternative for the treatment of the most problematic Gram-negative pathogens.     

Cancer mortality in Europe, 1995-1999, and an overview of trends since 1960

Mortality data, abstracted from the World Health Organization database, are presented in tabular form for 26 cancer sites or groups of sites, plus total cancer mortality, in 36 European countries during the period 1995-1999. Trends in mortality are also given in graphic form for 23 major countries plus the European Union as a whole over the period 1960-1999. In the European Union, total cancer mortality declined by 7% for both sexes over the last 5 years considered. The fall since the late 1980s was 10% in both sexes, corresponding to the avoidance of over 90000 deaths per year, as compared to the rates of the late 1980s. For the first time, over the last few years, some leveling of mortality was reported also in the Russian Federation, the Czech Republic, Poland, Hungary and other Eastern European countries, although cancer rates in those areas remain exceedingly high. The overall favorable pattern of cancer mortality over recent years is largely driven by the decline of tobacco-related cancer mortality in men. However, important components of the trends are also the persistence of substantial falls in gastric cancer, mainly in Russia and Eastern Europe, the recent decline in intestinal cancer in both sexes and of breast cancer in women, together with the long-term falls in uterine (cervical) cancer, leukemias, Hodgkin's disease and other neoplasms amenable to advancements in diagnosis and treatment. Female lung cancer mortality has been declining in the Russian Federation, but is still rising in other areas of the continent. Thus, urgent intervention is needed to bring under control the tobacco-related lung cancer epidemic in European women before it reaches the high level observed in North America. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html     

Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry

BACKGROUND: Tumor markers are becoming increasingly important in breast cancer research because of their impact on prognosis, treatment, and survival, and because of their relation to breast cancer subtypes. The triple-negative phenotype is important because of its relation to the basal-like subtype of breast cancer. METHODS: Using the population-based California Cancer Registry data, we identified women diagnosed with triple-negative breast cancer between 1999 and 2003. We examined differences between triple-negative breast cancers compared with other breast cancers in relation to age, race/ethnicity, socioeconomic status (SES), stage at diagnosis, tumor grade, and relative survival. RESULTS: A total of 6370 women were identified as having triple-negative breast cancer and were compared with the 44,704 women with other breast cancers. Women with triple-negative breast cancers were significantly more likely to be under age 40 (odds ratio [OR], 1.53), and non-Hispanic black (OR, 1.77) or Hispanic (OR, 1.23). Regardless of stage at diagnosis, women with triple-negative breast cancers had poorer survival than those with other breast cancers, and non-Hispanic black women with late-stage triple-negative cancer had the poorest survival, with a 5-year relative survival of only 14%. CONCLUSIONS: Triple-negative breast cancers affect younger, non-Hispanic black and Hispanic women in areas of low SES. The tumors were diagnosed at later stage and were more aggressive, and these women had poorer survival regardless of stage. In addition, non-Hispanic black women with late-stage triple-negative breast cancer had the poorest survival of any comparable group.     

重组人血管内皮抑素联合NP方案治疗晚期NSCLC随机、双盲、对照、多中心Ⅲ期临床研究

  目的   对比重组人血管内皮抑素(YH-16)联合GP方案与GP方案在治疗转移性三阴性乳腺癌中的有效性和安全性。   方法  55例转移性乳腺癌患者既往均经病理学诊断为三阴性浸润性导管癌, 均接受过紫杉类及蒽环类药物治疗。随机分为观察组及对照组, 其中观察组27例, 给予重组人血管内皮抑素联合GP方案治疗(重组人血管内皮抑素15 mg静脉滴注d1~14, 吉西他滨1 000mg/m²静脉滴注d1, 8;顺铂40mg/m²静脉滴注d1, 2);对照组28例, 仅给予GP方案化疗, 每3周为1个周期, 每2个周期评价疗效。   结果   55例患者均可评价疗效, 观察组(27例): 完全缓解(CR)3例(11.1%), 部分缓解(PR)9例(33.3%), 客观有效率(CR+PR)44.4%;对照组(28例): CR 1例(3.5%), PR 9例(32.1%), 客观有效率(CR+PR)35.7%。两组中位疾病进展时间分别为7.0、5.2个月, 无疾病进展生存比较有显著性差异(P=0.001)。不良反应主要为胃肠道反应及骨髓抑制, 两组比较无显著性差异(P > gt; 0.05)。   结论   重组人血管内皮抑素联合GP方案治疗转移性三阴性乳腺癌具有协同作用, 未增加不良反应, 可延长中位疾病进展时间, 值得进一步研究。     

Comparative In Vitro Activity of Sparfloxacin (AT 4140, RP 64206 - SPFX) Against 275 Multiresistant Clinical Isolates

The in-vitto activity of sparfloxacin was compared with that of pefloxacin, ofloxacin, ciprofloxacin, imipenem, ceftazidime, gentamicin and amikacin against 275 multiresistant nosocomial clinical isolates. They consisted of Pseudomonas aetuginosa (37), Entetobacter cloacae (42), Acinetobactet anitratus (60), Klebsiella pneumoniae (37) and Staphylococcus sp (99). Minimum inhibitory concentrations (MIC₉₀) and geometric mean MICs for sparfloxacin were as follows (mg/1): P. aeruginosa 128 - 23.7, E. cloacae 1 - 0.13, A. anitratus 2 - 0.14, K. pneumoniae 1 - 0.08, MRSA 16 - 0.98, MSSA 0.12 - 0.03, MRSE 0.25 - 0.12 and MSSE 0.12 - 0.05. It is concluded that sparfloxacin was the most potent agent against staphylococci and A. anitratus including strains resistant to the other quinolones while ciprofloxacin was the most potent agent against P. aeruginosa, E. cloacae and K. pneumoniae.     

Antimicrobial Activity of Daptomycin Tested Against Gram-Positive Strains Collected in European Hospitals: Results from 7 Years of Resistance Surveillance (2003-2009)

Abstract

Daptomycin is a cyclic lipopeptide approved by the European medicines Agency (EMEA) for the treatment of complicated skin and soft tissue infections (cSSTI) and Staphylococcus aureus bacteremia and endocarditis. We evaluated the in vitro activity of daptomycin and comparators tested against clinical isolates from European hospitals over a 7-year period (2003-2009). A total of 36,769 consecutive isolates were collected in 34 medical centers located in 13 European countries, turkey and Israel. the collection included S. aureus (18,352; 27.2% oxacillin-resistant [MRSA]); coagulase-negative staphylo-cocci (CoNS; 6,874), Enterococcus spp. (7,241; 9.4% vancomycin-resistant),β-hemolytic (3,009), viridans group streptococci (1,176), and Streptococcus bovis/gallolyticus (107). The organisms were isolated mainly from patients with bloodstream infection (56%) or cSSTI (23%). Daptomycin was very active against S. aureus and CoNS (MIC_50/90, 0.25/0.5 mg/L for both organisms), and its activity was not adversely influenced by oxacillin resistance. All Enterococcus faecalis strains were susceptible to daptomycin (MIC_50/90, 1/1 mg/L). Daptomycin (MIC_50/90, 2/2 mg/L; 100.0% susceptible) and linezolid (MIC_50/90, 1/2 mg/L; 99.7% susceptible) were the most active agents tested against vancomycin-resistant E. faecium. Vancomycin-resistant and -susceptible enterococcal strains were equally susceptible to daptomycin. Daptomycin was also active against β-hemolytic streptococci (MIC_50/90, 0.06/0.25 mg/L; 100.0% susceptible), viridans group streptococci (MIC_50/90, 0.25/0.5 mg/L; 99.8% susceptible) and S. bovis (MIC_50/90, 0.06/0.12 mg/L; 100.0% susceptible).

In summary, daptomycin was very potent against this large collection (36,769) of Gram-positive organisms isolated in European hospitals, and its activity remained stable across the 7-year period evaluated (2003-2009), using reference methods and interpretive criteria. Decreases in daptomycin potency were not observed since EMEA approval and widespread clinical use, and emerging resistance to other compounds did not adversely influence daptomycin activity against contemporary Gram-positive species.     

Antimicrobial Spectrum and Potency of Dalbavancin Tested Against Clinical Isolates from Europe and North America (2003): Initial Results from an International Surveillance Protocol

Abstract

Dalbavancin is a bactericidal dimethylaminopropyl amide glycopeptide derivative possessing an extended serum elimination half-life in humans that allows onceweekly dosing for the therapy of Gram-positive infections. Strains from this baseline surveillance protocol in North America (NA; USA and Canada) and Europe (EU, 14 countries) were sampled in 2003. A total of 7,765 Gram-positive isolates (3,695 from NA and 4,070 from EU) were tested by reference broth microdilution methods against dalbavancin and 10 comparator agents. Species were analyzed separately by resistance phenotypes such as methicillin- (oxacillin-) resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and penicillin- resistant Streptococcus pneumoniae. Dalbavancin and other glycopeptides were very active against staphylococci (n=4648) with dalbavancin being 16- to 32- fold more potent than vancomycin (MIC₉₀, 0.06 versus 2 mg/L). MRSA rates were greater (31.6%) in NA than in EU (26.1%). Quinupristin/dalfopristin resistance (MIC, ≥ 2 mg/L; 0.1 - 0.5%) was documented more often in EU compared to NA. Dalbavancin (MIC₅₀, 0.03 - 0.06 mg/L) was active against enterococci, except VanA resistance phenotypes. VRE rates were lower in EU (8.3%) then in NA (35.9%) from this resistance-enhanced enterococcal collection. Streptococci (dalbavancin MIC₉₀, 0.016 - 0.03 mg/L) were generally most susceptible to glycopeptides (100.0%), quinupristin/dalfopristin (98.6 - 100.0%) and linezolid (100.0%); but dalbavancin was 16-fold more active than comparators. All vancomycin-susceptible enterococci and > 90% of vanB VRE had dalbavancin MIC values at ≤ 1 mg/L, but vanA VRE strains had dalbavancin MIC results ranging from 0.06 to > 8 mg/L (median MIC, ≥ 8 mg/L). Dalbavancin MIC values were not adversely influenced by geographic region or resistance phenotype (except vanA VRE). Infrequently isolated Gram-positive organisms such as Bacillus spp. (MIC₉₀, 0.12 mg/L), Corynebacterium spp. (MIC₉₀, 0.12 mg/L), Listeria monocytogenes (MIC₉₀, 0.25 mg/L) and Micrococcus spp. (MIC₉₀, 0.03 mg/L) were very susceptible to dalbavancin. In conclusion, these 2003 baseline resistance surveillance findings confirm the potent dalbavancin activity compared to several comparator agents against important Gram-positive pathogens. This high volume international survey indicates potential therapeutic roles for dalbavancin against many troublesome resistant Gram-positive phenotypes.     

In Vitro Activity of Cefpirome (HR 810) against Enterococci and Staphylococci

Summary

The inhibitory activity of cefpirome (HR 810), a new cephalosporin derivative for parenteral use, was tested by agar dilution methods against Enterococcus faecatis (100 strains), Staphylococcus aureus (40 strains) and coagulase-negative staphylococcal species (60 strains) in comparison with other beta-lac ta m antibiotics.

For E. faecalls, the cefpirome minimum inhibitory concentration (MIC) range was 2-128 μg/ml, with an MIC,, of 8 μg/ml, and an MIC₉₀, of 64 μg/ml. The optimal bactericidal activity against strains with MICs of ≤ 8 μg/ml occurred at 2-4 times the MIC, and the reduction in the initial inoculum was 99.9-99.7% after 24 h incubation at these concentrations.

Mec gene-negative staphylococci (both S. aureus and coagulase- negative species) had cefpirome MICs of 0.25-2 μg/ml (MIC₅₀ 0.5 μg/ml, MIC₉₀ 1 μg/ml). Mec gene-positive strains had MICs of 0.5-128 μg/ml (MIC₅₀ 2 μg/ml, MIC₉₀ 32 μg/ml). Strains with borderline resistance to oxacillin which did not harbor the mec gene and which were susceptible to cefpirome maintained their susceptibility even when high-density inocula were used and after several passages in media containing the antibiotic.

These studies present some potential advantages of cefpirome over other cephalosporins in the inhibitory activity against Gram-positive cocci.