Evaluation of in vitro interaction of daptomycin with gentamicin or beta-lactam antibiotics against Staphylococcus aureus and Enterococci by FIC index and timed-kill curves

The interactions of daptomycin with gentamicin and 5 beta-lactam agents were determined by checkerboard and timed-kill studies. Eighty isolates were tested by checkerboard: 20 each of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), vancomycin-susceptible Enterococcus faecalis (VSEF) and vancomycin-resistant enterococci (VRE). Time kill curves were performed on 8 selected isolates: 2 each of MRSA, MSSA, VSEF and VRE. Checkerboard results showed highest frequency of synergistic effects against VSEF (35-75%) with daptomycin combined with ceftriaxone, cefepime or imipenem; a modest effect with most combinations against VRE and MRSA (5-20%); and indifference with daptomycin and most agents against MSSA (0-5%); except with daptomycin with oxacillin where 10-20% synergy was observed. Synergistic interaction was confirmed by time kill studies in seven of ten isolates where checkerboard suggested synergy. A bactericidal effect was exerted in 5/7 synergistic combinations. The in vitro data suggest that daptomycin combined with other antibiotics may be microbiologically beneficial and not antagonistic.     

In vitro activities of antimicrobial cationic peptides; melittin and nisin,alone or in combination with antibiotics against Gram-positive bacteria

Abstract

The in vitro activities of two antimicrobial cationic peptides, melittin and nisin alone and in combination with frequently used antibiotics (daptomycin, vancomycin, linezolid, ampicillin, and erythromycin), were assessed against clinical isolates of methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Enterococcus faecalis. Using the broth microdilution method, minimum inhibitory concentration (MIC) ranges of melittin and nisin against all strains were 2–8 μg/ml and 2–32 μg/ml respectively. In combination studies performed with the microdilution checkerboard method using a fractional inhibitory concentration index of ?0·5 as borderline, synergistic interactions occurred more frequently with nisin–ampicillin combination against MSSA and nisin–daptomycin combination against E. faecalis strains. The results of the time-killing curve analysis demonstrated that the concentration dependent rapid bactericidal activity of nisin, and that synergism or early synergism was detected in most strains when nisin or melittin was used in combination with antibiotics even at concentrations of 0·5×MIC.     

Versatility of targeted antibiotic-loaded gold nanoconstructs for the treatment of biofilm-associated bacterial infections

Abstract

Background: We previously demonstrated that a photoactivatable therapeutic approach employing antibiotic-loaded, antibody-conjugated, polydopamine (PDA)-coated gold nanocages (AuNCs) could be used for the synergistic killing of bacterial cells within a biofilm. The approach was validated with a focus on Staphylococcus aureus using an antibody specific for staphylococcal protein A (Spa) and an antibiotic (daptomycin) active against Gram-positive cocci including methicillin-resistant S. aureus (MRSA). However, an important aspect of this approach is its potential therapeutic versatility.

Methods: In this report, we evaluated this versatility by examining the efficacy of AuNC formulations generated with alternative antibodies and antibiotics targeting S. aureus and alternative combinations targeting the Gram-negative pathogen Pseudomonas aeruginosa.

Results: The results confirmed that daptomycin-loaded AuNCs conjugated to antibodies targeting two different S. aureus lipoproteins (SACOL0486 and SACOL0688) also effectively kill MRSA in the context of a biofilm. However, our results also demonstrate that antibiotic choice is critical. Specifically, ceftaroline and vancomycin-loaded AuNCs conjugated to anti-Spa antibodies were found to exhibit reduced efficacy relative to daptomycin-loaded AuNCs conjugated to the same antibody. In contrast, gentamicin-loaded AuNCs conjugated to an antibody targeting a conserved outer membrane protein were highly effective against P. aeruginosa biofilms.

Conclusions: These results confirm the therapeutic versatility of our approach. However, to the extent that its synergistic efficacy is dependent on the ability to achieve both a lethal photothermal effect and the thermally controlled release of a sufficient amount of antibiotic, they also demonstrate the importance of carefully designing appropriate antibody and antibiotic combinations to achieve the desired therapeutic synergy.     

Determination of synergy between sulbactam,meropenem and colistin in carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii isolates and correlation with the molecular mechanism of resistance

Treatment of infections with carbapenem-resistant Gram negative organism is a major challenge especially among intensive care patients. Combinations of sulbactam, meropenem and colistin was studied for its synergistic activity against 100 invasive isolates of carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii-calcoaceticus complex by checkerboard assay and time kill assay (TKA). In addition, presence of carbapenemase production was determined by multiplex PCR. Time kill assay detected more synergy than checkerboard assay. Good bactericidal activity of 70–100% was noted with the combinations tested. Among K. pneumoniae, isolates producing NDM carbapenemase alone showed significantly more synergy than isolates producing OXA-48-like carbapenemases. In treatment of infection with carbapenem-resistant organisms, the site of infection and the type of carbapenemase produced may help to determine the most effective combination of antimicrobials.     

In vitro activity of daptomycin alone and in combination with various antimicrobials against Gram-positive cocci

The increasing prevalence of resistant Gram-positive cocci requires the need to search for more effective agents and synergistic combinations. Forty-two vancomycin-resistant Enterococcus faecium (VREF), 30 methicillin-resistant Staphylococcus aureus (MRSA) and 36 Staphylococcus epidermidis (MRSE) strains were studied. Minimum inhibitory concentrations (MICs) were determined and synergy testing was performed by using E test for daptomycin, ampicillin-sulbactam, piperacillin-tazobactam and ticarcillin-clavulanate against staphylococci; for daptomycin, ampicillin, rifampin, and gentamicin against enterococci. Daptomycin in combination with ampicillin, rifampin, and gentamicin was tested against enterococci; daptomycin in combination with ampicillin-sulbactam, piperacillin-tazobactam, and ticarcillin-clavulanate was tested against staphylococci. Interaction categories were defined by the fractional inhibitory concentration (FIC) index. All strains of staphylococci and enterococci were susceptible to daptomycin. All three combinations showed synergy against more than 70% of the MRSA strains. Daptomycin in combination with ampicillin, rifampin, and gentamicin against enterococci showed synergies of 64.2%, 57.1% and 21.4%, respectively. This study indicates that daptomycin alone and combined with beta-lactams seems to be effective against MRSA, but further in vitro and in vivo studies on the subject are required before clinical use can be recommended.     

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 resistance among Gram-positive pathogens in Saudi Arabia

Abstract

Several species of Gram-positive cocci are major nosocomial or community pathogens associated with morbidity and mortality. Here, we review the antimicrobial resistance among these pathogens in Saudi Arabia. In the last decades, antimicrobial resistance has increased among Staphylococcus aureus in the Kingdom with a growing prevalence of both nosocomial and community methicillin-resistant S. aureus (MRSA) isolates. As yet, no vancomycin-resistant MRSA have been reported, although isolates with reduced susceptibility to the drug have been noted. Currently, the prevalence of vancomycin-resistant entrococci (VRE) is low; however, VRE has been described in the Kingdom as well as Enterococcus faecalis and E. faecium isolates with high-level resistance to penicillin, sulfamethoxazole, macrolides, tetracycline, and aminoglycosides. In recent decades, the prevalence and rate of penicillin resistance and non-susceptibility among Streptococcus pneumoniae isolates have increased in Saudi Arabia. The organism remains, however, susceptible to other beta-lactams and to quinolones. On the other hand, resistance to co-trimoxazole and tetracyclines is high and resistance to macrolides is on the increase.     

In-vitro activity of ceftriaxone combined with newer agents against MRSA

In this study, in vitro synergism in combinations of agents as ceftriaxone/dalbavancin, ceftriaxone/linezolid and ceftriaxone/daptomycin against MRSA strains were investigated. Thirty clinical MRSA strains were tested. The minimum inhibitory concentrations of all antibiotics were determined using reference broth microdilution method. In-vitro activities of antibiotics combined against the strains were tested using two-dimensional checkerboard microdilution method. Results were interpreted as follows: synergy = FICI ≤0.5; ‘no interaction’ effect = FICI ?0.5-≤4; antagonism = FICI ?4. The MIC₅₀, MIC₉₀ and MIC_range of ceftriaxone, daptomycin, dalbavancin and linezolid were found as 128, 1024 and 16-2048 mg/L; 1, 1 and 0.5–1 mg/L; 0.12, 0.12 and 0.03–0.12 mg/L; and 1, 2 and 1–2 mg/L, respectively. Our results showed that the frequency of synergistic effects (FICI: ≤0.5) of three combinations were all at the same rate of 77% (23/30). No in vitro antagonism (FICI >4) was observed.     

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.     

mecA-positive methicillin-sensitive Staphylococcus aureus clinical isolates in Zenica-Doboj Canton,Bosnia and Herzegovina

Forty-four mecA-positive and eight mecA-negative Staphylococcus aureus isolates confirmed by PCR were further tested by disc-diffusion (DD) oxacillin and cefoxitin, oxacillin Epsilon (E)-test, and oxacillin and cefoxitin minimal inhibitory concentration (MIC) Strip methicillin-resistant phenotype in S. aureus (MRSA) tests. Among 44 mecA-positive S. aureus isolates, two (4·5%) were detected as MRSA by DD-oxacillin, 17 (38·6%) by DD-cefoxitin test, and seven (15·9%) by the E-test. In the cefoxitin MIC Strip MRSA test, 19 (43·2%) isolates were resistant. In the oxacillin MIC Strip MRSA test, 18 (40·9%) isolates were resistant and 26 (59·1%) were sensitive, i.e. oxacillin-sensitive MRSA (OS-MRSA) (MIC range 0·25-≤0·25 mg/l). Fifteen out of 26 OS-MRSA (57·7%) belonged to spa-CC 355/595, 78% of which belonged to the largest PFGE clone. Some discrepancies between the phenotypic methods for MRSA identification obtained in this study were caused by large proportion of OS-MRSA. Misidentification of OS-MRSA as MSSA might result in an appearance of highly resistant MRSA in patients treated with beta-lactam antibiotics.     

Daptomycin In Vitro Activity Tested Against Gram-Positive Strains Collected from European and Latin American Medical Centers in 2003

Abstract

Daptomycin, a cyclic lipopeptide, was susceptibility tested against clinical bacterial isolates consecutively collected in hospitals located in Europe (4,731 strains) and Latin America (1,007 strains) in 2003 as part of a continuing surveillance program. The bacterial isolates tested were Gram-positive pathogens that included staphylococci, streptococci and enterococci. The isolates were tested for susceptibility using broth microdilution methods (broth with 50 mg/L Ca⁺⁺ for testing daptomycin). All isolates, except two Enterococcus faecium strains from Europe, were inhibited at daptomycin MIC of ≤4 mg/L. In addition, 99.4 and 97.3% of isolates were inhibited at daptomycin MIC of ≤2 and ≤1 mg/L, respectively. Except for one Staphylococcus aureus and one viridans group streptococci from Europe and one coagulase-negative staphylococci from Latin America, all staphylococcal and streptococcal isolates were inhibited by 1 mg/L of daptomycin. Resistance to other compounds (vancomycin, oxacillin, and penicillin) did not influence daptomycin activity. The activity of daptomycin was very similar in both geographic regions evaluated and demonstrated the same MIC distribution as isolates evaluated in studies in the United States. The results of this study showed that daptomycin continues to be very active against clinical isolates of Gram-positive cocci isolated in Europe and Latin America.     

Ceftaroline fosamil and treatment of acute bacterial skin and skin structure infections: CAPTURE study experience

Abstract

The Clinical Assessment Program and TEFLARO Utilization Registry (CAPTURE) is a multicentre retrospective cohort study in the USA describing treatment of acute bacterial skin and skin structure infection (ABSSSI) with ceftaroline fosamil (CPT-F). Charts for review were chosen by random selection. Among 647 evaluable patients, 52% were obese, 46% had diabetes mellitus (DM), and 19% had peripheral vascular disease (PVD). Methicillin-resistant Staphylococcus aureus (MRSA) was recovered in 28% and methicillin-susceptible S. aureus (MSSA), 11%. Antibiotics were administered prior to CPT-F treatment in 80%, and concurrently in 39%. Clinical success overall was 85%; in patients with DM, 83%; with PVD, 76%; and in obese patients, 88%. Clinical success was ≧ 79% across all infection types; 81% for MRSA and 83% for MSSA; and 86% for ceftaroline monotherapy and 84% for concurrent therapy. These high clinical success rates support CPT-F as an effective treatment option for ABSSSI, including infections due to MRSA and patients with significant co-morbidities.     

Genetic lineages and antimicrobial resistance genotypes in Staphylococcus aureus from children with atopic dermatitis: detection of clonal complexes CC1, CC97 and CC398

The objective was to analyse the genetic lineages of Staphylococcus aureus recovered from nasal and skin samples of atopic dermatitis (AD) paediatric patients, and to characterize the antimicrobial resistance phenotype–genotype and the immune-evasion-cluster (IEC) type of isolates. Forty S. aureus isolates from 35 patients (skin: 26; nasal samples: 14) were characterized. Isolates were submitted to spa-, agr- and multilocus sequence typing. All S. aureus strains analyzed were methicillin-susceptible (MSSA). High genetic diversity was detected among the 40 MSSA isolates (especially among skin isolates), with detection of 27 different spa-types, 20 sequence-types and 16 clonal complexes (CCs). Lineages CC30 and CC5 were predominant among nasal isolates (71% vs 23% skin). Thirteen different CCs were detected among skin isolates, with detection of clades CC1, CC9 and CC398. Antimicrobial resistance rates detected were higher in skin than in nasal isolates, especially for macrolides, aminoglycosides, lincosamides and mupirocin. MSSA strains were characterized into five IEC-types, being A, B and F the predominant ones. MSSA strains of lineages CC45 and CC5 were detected in almost all cases in AD patients with severe Scoring Atopic Dermatitis (SCORAD) and lineages CC8, and CC30 in those with mild or moderate one. As conclusion, high-clonal-diversity was detected among MSSA from AD patients, especially in skin-isolates. Colonization with S. aureus of some CCs seems more associated with AD severity than other lineages.     

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 activities of imipenem–colistin,imipenem–tigecycline,and tigecycline–colistin combinations against carbapenem-resistant Enterobacteriaceae*

The aim of the study is to determine in-vitro effects of imipenem–tigecycline, imipenem–colistin and tigecycline–colistin against carbapenem-resistant Enterobacteriaceae (CRE) isolates. A total of 25 CRE isolates were included to the study. The minimum inhibition concentrations of imipenem, colistin-sulphate and tigecycline were determined with broth dilution method. Synergistic effects of imipenem–tigecycline, imipenem–colistin and tigecycline–colistin were investigated by microdilution checkerboard technique. All of the isolates were resistant to imipenem, whereas 25% of the isolates were resistant to colistin and tigecycline. Imipenem–colistin, imipenem–tigecycline and tigecycline–colistin combinations were synergistic against 40% (10/25), 24% (6/25), and 36% (9/25) of the isolates, respectively. Antagonism was observed in 8% (2/25) of the isolates in tigecycline–colistin combination. Tigecycline–colistin was the most effective (70% synergy) combination in Klebsiella spp. strains; whereas imipenem–colistin was the most effective (75% synergy) combination in Escherichia coli strains. Synergistic effect was variable and strain-depended against CRE isolates that have been tested.     

Predominance of hospital-associated MRSA among cystic fibrosis patients in a Turkish reference cystic fibrosis centre

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) strains are the major causative agents of numerous hospital- and community-acquired infections. Increasing prevalence of MRSA in cystic fibrosis (CF) populations is reported all over the world. Although there are papers reporting the prevalence and genetic backgrounds of MRSA isolates from different settings in Turkey, there is no information regarding the situation in the CF community. This study was conducted to characterize the MRSA strains recovered from CF patients followed-up at a Turkish reference CF centre. Microbiological testing of isolates was performed via conventional microbiological techniques. Molecular characterization of MRSA isolates was carried out by SCCmec typing by multiplex PCR and PVL gene determination. Among a total of 604 CF patients included in the study, 325 patients were found to harbour S. aureus (53·8%). Of those 325 patients, 24 were positive for MRSA during their follow-up (7·4%). Thirty-two MRSA isolates from these patients were chosen for further assessment of molecular characteristics. Twenty-six MRSA isolates exhibited a pattern like SCCmec type III (81·2%) and six consecutive MRSA isolates of a single patient revealed SCCmec type IV (18·7%). Our findings definitely support the need for further surveillance studies for CF-MRSA strains and highlight the need for infection control measures in the setting of CF centres.     

Activity of ceftaroline and comparator agents tested against contemporary Gram-positive and -negative (2011) isolates collected in Europe,Turkey, and Israel

Abstract

The activity of ceftaroline was tested against 8233 isolates mainly collected from bloodstream, urinary, respiratory and skin and soft tissue specimens in European medical centers during 2011. This cephalosporin displayed activity against Staphylococcus aureus (MIC₅₀, 0·25 mg/l), with greater activity against MRSA (MIC₅₀, 1 mg/l) than other β-lactams tested. Against Streptococcus pneumoniae, including penicillin-resistant strains, other streptococcal groups and Haemophilus spp., ceftaroline was highly active and MIC90 values ranged from ≤0·015 to 0·12 mg/l. Ceftaroline, like other cephalosporins, had limited activity against ESBL-phenotype Enterobacteriaceae, but showed good activity against isolates not displaying an ESBL-phenotype. Ceftaroline remains very active against MRSA and other organisms than could be associated with its approved indications in the EU (complicated skin and soft tissue infections and community-acquired pneumonia).     

Influence of Human Ascitic Fluid on the In Vitro Antibacterial Activity of Moxifloxacin

Abstract

We investigated the in vitro influence of HAF on the antibacterial activity of moxifloxacin against Escherichia coli ATCC 10798, Escherichia coli K-12, Proteus rettgeri (Sanelli), Staphylococcus aureus ATCC 25923 Staphylococcus aureus NCTC 1808 and Staphylococcus epidermidis ATCC 12228. Human ascitic fluid was obtained from 6 cirrhotic patients by paracentesis. The interaction effect was evaluated by the checkerboard technique. Our results indicate the ability of human ascitic fluid to reduce minimum inhibitory concentrations of moxifloxacin against Gram-negative bacteria, but not against Gram-positives.     

In vitro combined effects of cefozopran/teicoplanin and cefozopran/vancomycin on methicillin-resistant Staphylococcus aureus

We determined the in vitro effects of teicoplanin (TEIC) or vancomycin (VCM) added to cefozopran (CZOP) on 50 methicillin-resistant Staphylococcus aureus (MRSA) strains, using a modified checkerboard method with serial 1.25-fold dilutions, and assessed the time-kill curve. CZOP + TEIC was synergistic (fractional inhibitory concentration index < or = 0.5) against 98% and CZOP + VCM against 20% of strains. Both drug combinations were additive against the remaining strains. A comparison of the fractional bactericidal concentration indices for 32 strains showed synergistic bactericidal effects for CZOP + TEIC in 88%, and in 48% for CZOP +VCM, confirming that CZOP + TEIC is superior to CZOP + VCM. The time-kill curve confirms that the bactericidal potency of these drugs is increased through combined use with CZOP. These results suggest that treatment using TEIC or VCM with CZOP may be useful in treating MRSA infections, including polymicrobial infections and those involving Gram-negative rods.     

Telavancin activity tested against Gram-positive clinical isolates from European,Russian and Israeli hospitals (2011–2013) using a revised broth microdilution testing method: redefining the baseline activity of telavancin

Objectives: To reassess the activity of telavancin when tested against Gram-positive clinical pathogens recovered from hospitalized patients in European and adjacent regions using a revised broth microdilution method.

Methods: 11?601 consecutive, non-duplicate isolates originating from 36 institutions among 18 countries recovered between 2011 and 2013 were tested for susceptibility using a revised broth microdilution method for telavancin. Interpretive telavancin breakpoints appropriate for the method were those recently approved by the FDA and EUCAST, as available.

Results: Telavancin (MIC_50/90, 0.03/0.06?mg/l; 100.0% susceptible) was equally potent against methicillin-susceptible ((MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus. All Enterococcus faecalis was susceptible to telavancin (MIC_50/90, 0.12/0.12?mg/l) and inhibited at the susceptibility breakpoint (i.e. ≤?0.25?mg/l), except for VanA-phenotype vancomycin-resistant isolates (telavancin MIC, >1?mg/l). Telavancin (?≤?0.015/0.03?mg/l) was active against vancomycin-susceptible Enterococcus faecium, while higher MIC values were obtained for VanA strains. Telavancin (both MIC₅₀ and MIC₉₀, ≤?0.015?mg/l) was potent against Streptococcus pneumoniae, beta-haemolytic streptococci (MIC_50/90, ≤?0.015/0.06?mg/l) and viridans group streptococci (MIC_50/90, ≤?0.015/0.03?mg/l).

Conclusions: Telavancin exhibited potent activity against this contemporary (2011–2013) collection of organisms, inhibiting indicated pathogens at or below the FDA/EUCAST-approved breakpoints for susceptibility. VanA-phenotype enterococci were less susceptible to telavancin, a feature observed using the previous testing method. These results redefine telavancin's activity against isolates from Europe.