RESUMEN
Oritavancin exhibited in vitro activity against 169 strains of vancomycin-susceptible, methicillin-resistant Staphylococcus aureus (MRSA) with MICs ranging from 0.03 to 1 µg/ml and against vancomycin-intermediate MRSA (VISA; n = 29), heterogeneous vancomycin-intermediate MRSA (hVISA; n = 5), and vancomycin-resistant MRSA (n = 5) strains, with MICs ranging from 0.12 to 4 µg/ml. For 10 MRSA isolates comprising 5 VISA and 5 hVISA strains, synergy between oritavancin and gentamicin, linezolid, or rifampin was observed against most of the strains tested using a time-kill method.
Asunto(s)
Antibacterianos/farmacología , Glicopéptidos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Sinergismo Farmacológico , Lipoglucopéptidos , Pruebas de Sensibilidad MicrobianaRESUMEN
The past decade has seen an alarming confluence of circumstances antithetical to development of new antibacterials, and most of the very few new drugs under development have problems with their microbiology, toxicity, or pharmacokinetics and pharmacodynamics. Most large pharmaceutical companies have divested themselves of their antibiotic portfolios, and the promise that start-up companies would fill the niche has not been fulfilled. What is left of the field is being stifled by bureaucratic regulations, problems with approval, lack of expertise and a general lack of understanding of how serious the situation is. In paediatrics, in particular, there is no sign of any new antibacterial in the foreseeable future. Waiting for initiatives and deliberations will probably take too long, and a vigorous and deliberate effort to educate the public-who in their turn can apply the needed pressure--seems to be the only way of achieving a rapid turnaround of this most dangerous situation.
Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Farmacorresistencia Bacteriana , Antibacterianos/uso terapéutico , Infecciones Bacterianas/mortalidad , Aprobación de Drogas , Descubrimiento de Drogas/tendencias , Humanos , Incidencia , Insuficiencia del TratamientoRESUMEN
OBJECTIVES: To characterize the mechanisms responsible for elevated MICs of ceftaroline for methicillin-resistant Staphylococcus aureus (MRSA). METHODS: During the 2008 Assessing Worldwide Antimicrobial Resistance Evaluation ('AWARE') surveillance programme, four S. aureus collected from separate patients in Athens, Greece, demonstrated ceftaroline MICs of 4 mg/L. These isolates were clonally related and one strain (13101) was selected for further characterization. Two strains (4981 and 4977) displaying ceftaroline MICs of 1 and 2 mg/L, respectively, were included for comparison. All strains originated from the same hospital. Penicillin-binding protein (PBP) affinities for ceftaroline and comparators were determined. Strains were typed by single-locus typing (i.e. spa typing), multilocus sequence typing ('MLST') and by multiple-locus variable-number tandem repeat fingerprinting (MLVF). The presence of Pantone-Valentine leucocidin and the staphylococcal cassette chromosome mec types was assessed. We also performed nucleotide sequencing of the mecA (encoding PBP2a) promoter and ribosomal binding site (rbs) regions and mecR1. RESULTS: Ceftaroline demonstrated the highest PBP2a affinity with strain 4981 (ST5-MRSA-II) (IC(50) 0.06 mg/L; MIC 1 mg/L). Strains 4977 and 13101 (both ST239-MRSA-III) showed indistinguishable MLVF profiles. Ceftaroline PBP2a binding affinity in strains 4977 (IC(50) 0.25 mg/L; MIC 2 mg/L) and 13101 (IC(50) 1 mg/L; MIC 4 mg/L) was 4- and 16-fold lower than 4981, respectively. Strain 4981 contains a wild-type PBP2a, while strains 4977 and 13101 have N(146)K and E(150)K alterations in the non-penicillin-binding domain. Additionally, 13101 has one substitution (H(351)N) in the transpeptidase domain. Alterations in the mecR1, mecA promoter or rbs regions were not observed. CONCLUSIONS: Increased ceftaroline MICs were associated with decreased PBP2a binding affinity and reflected alterations in PBP2a.
Asunto(s)
Antibacterianos/farmacología , Cefalosporinas/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Estafilocócicas/microbiología , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Toxinas Bacterianas/genética , Dermatoglifia del ADN , Exotoxinas/genética , Genotipo , Grecia , Humanos , Leucocidinas/genética , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Tipificación Molecular , Proteínas de Unión a las Penicilinas/metabolismo , Unión Proteica , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Factores de Virulencia/genética , CeftarolinaRESUMEN
BACKGROUND: Emergence of multidrug-resistant Staphylococcus aureus has triggered a reassessment of fusidic acid (CEM-102, sodium fusidate). METHODS: Fusidic acid was examined for (1) activity against recent methicillin-resistant S. aureus (MRSA) isolates; (2) modulation of activity by acidic pH; and (3) accumulation by phagocytic cells and intracellular activity against methicillin-susceptible S. aureus (MSSA) and MRSA. RESULTS: About 96% of strains (N = 94) were susceptible (European Committee on Antimicrobial Susceptibility Testing breakpoint [≤ 1 mg/L]). Activity was enhanced at pH 5.5 (6 dilutions decrease for minimum inhibitory concentration) in parallel with an increase of drug bacterial accumulation (opposite effects for clindamycin; linezolid remained unaffected). Fusidic acid accumulated in THP-1 cells (about 5.5 fold), with further accumulation at pH 5.5 vs pH 7.4. The intracellular activity of Fusidic acid was similar to that of clindamycin and linezolid (maximal relative activity, 0.4-0.6 log(10) colony-forming unit decrease). No cross-resistance to vancomycin or daptomycin was observed. CONCLUSIONS: Fusidic acid is active against S. aureus in broth as well as intracellularly, with no cross-resistance to other antibiotics.
Asunto(s)
Antibacterianos/farmacología , Ácido Fusídico/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Monocitos/microbiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Acetamidas/farmacología , Línea Celular , Clindamicina/farmacología , Recuento de Colonia Microbiana , Medios de Cultivo , Humanos , Concentración de Iones de Hidrógeno , Linezolid , Meticilina/farmacología , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana/normas , Monocitos/efectos de los fármacos , Oxazolidinonas/farmacología , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
Ceftaroline, the active component of the prodrug ceftaroline fosamil, is a novel broad-spectrum cephalosporin with bactericidal activity against Gram-positive and -negative isolates. This study evaluated the potential for ceftaroline and comparator antibiotics to select for clones of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis with elevated MICs. S. pneumoniae and S. pyogenes isolates in the present study were highly susceptible to ceftaroline (MIC range, 0.004 to 0.25 µg/ml). No streptococcal strains yielded ceftaroline clones with increased MICs (defined as an increase in MIC of >4-fold) after 50 daily passages. Ceftaroline MICs for H. influenzae and M. catarrhalis were 0.06 to 2 µg/ml for four strains and 8 µg/ml for a ß-lactamase-positive, efflux-positive H. influenzae with a mutation in L22. One H. influenzae clone with an increased ceftaroline MIC (quinolone-resistant, ß-lactamase-positive) was recovered after 20 days. The ceftaroline MIC for this isolate increased 16-fold, from 0.06 to 1 µg/ml. MICs for S. aureus ranged from 0.25 to 1 µg/ml. No S. aureus isolates tested with ceftaroline had clones with increased MIC (>4-fold) after 50 passages. Two E. faecalis isolates tested had ceftaroline MICs increased from 1 to 8 µg/ml after 38 days and from 4 to 32 µg/ml after 41 days, respectively. The parental ceftaroline MIC for the one K. pneumoniae extended-spectrum ß-lactamase-negative isolate tested was 0.5 µg/ml and did not change after 50 daily passages.
Asunto(s)
Antibacterianos/farmacología , Cefalosporinas/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Enterococcus faecalis/efectos de los fármacos , Haemophilus influenzae/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacos , CeftarolinaRESUMEN
Against 33 Gram-positive and -negative bacteria, NXL 103 MICs were 0.03 to 1 µg/ml. NXL 103 was bactericidal by 12 h at 2 × MIC against all 5 pneumococci and at 2 × MIC after 24 h against all 5 group A and B ß-hemolytic streptococci. NXL 103 was bactericidal against all 8 Haemophilus influenzae strains at 2 × MIC and all 5 Moraxella catarrhalis strains at 4 × MIC after 24 h but was mainly bacteriostatic against 5 methicillin-resistant Staphylococcus aureus strains. After the exposure of one strain of each species to NXL 103 for 10 daily subcultures, the MICs remained within ± 1 dilution.
Asunto(s)
Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Estreptograminas/farmacología , Haemophilus influenzae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacosRESUMEN
We tested the MICs of fusidic acid (CEM-102) plus other agents against 40 methicillin-resistant Staphylococcus aureus (MRSA) isolates from cystic fibrosis patients and the activities of fusidic acid with or without tobramycin or amikacin against Pseudomonas aeruginosa, MRSA, and Burkholderia cepacia isolates from cystic fibrosis patients in a 24-h time-kill study. Fusidic acid was potent (MICs, 0.125 to 0.5 µg/ml; a single 500-mg dose of fusidic acid at 8 h averaged 8 to 12. 5 µg/ml with 91 to 97% protein binding) against all MRSA strains. No antagonism was observed; synergy occurred for one MRSA strain treated with fusidic acid plus tobramycin.
Asunto(s)
Amicacina/farmacología , Burkholderia cepacia/efectos de los fármacos , Fibrosis Quística/microbiología , Ácido Fusídico/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Tobramicina/farmacología , Sinergismo Farmacológico , HumanosRESUMEN
ACHN-490 was tested alone and in combination with cefepime, doripenem, imipenem, or piperacillin-tazobactam in a synergy time-kill analysis against 25 Pseudomonas aeruginosa strains with different resistance phenotypes. Each combination was synergistic against most isolates at 24 h, and antagonism was not observed. Combinations of ACHN-490 with cefepime, doripenem, imipenem, or piperacillin-tazobactam yielded synergies in ≥70% and ≥80% of strains at 6 and 12 h, respectively, and in ≥68% at 24 h.
Asunto(s)
Antibacterianos/farmacología , Carbapenémicos/farmacología , Cefalosporinas/farmacología , Imipenem/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Cefepima , Doripenem , Pruebas de Sensibilidad Microbiana , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/farmacología , Piperacilina/farmacología , Combinación Piperacilina y TazobactamRESUMEN
BACKGROUND: Co-trimoxazole, clindamycin and linezolid are used to treat community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, but little is known about intracellular activity. Moxifloxacin is active against intracellular methicillin-susceptible S. aureus (MSSA), but CA-MRSA has not been studied. METHODS: We used 12 clinical CA-MRSA, 1 MSSA overexpressing norA and 2 hospital-acquired MRSA (moxifloxacin MICs: 0.03 to 4 mg/L). Activity was assessed in broth and after phagocytosis by THP-1 macrophages or keratinocytes {concentration-dependent experiments [24 h of incubation] to determine relative potencies [EC(50)], static concentrations [C(s)] and maximal relative efficacies [E(max) (change in log(10) cfu compared with initial inoculum)] and time-dependent experiments [0-72 h] at human C(max)}. RESULTS: Concentration-dependent experiments: in broth, EC(50) and C(s) were correlated with the MIC for all antibiotics, but moxifloxacin achieved significantly (Pâ<â0.01) greater killing (more negative E(max)) than the comparators; and in THP-1 cells and keratinocytes, moxifloxacin acted more slowly but still reached a near bactericidal effect (2 to 3 log(10) cfu decrease) at 24 h with unchanged EC(50) and C(s) as long as its MIC was ≤0.125 mg/L (recursive partitioning analysis). Clindamycin and linezolid were static, and co-trimoxazole was unable to suppress the intracellular growth of CA-MRSA. At human C(max) in broth, moxifloxacin killed more rapidly and more extensively (≥5 log(10) cfu decrease at 10 h) than clindamycin (4 log(10) cfu at 48 h) or co-trimoxazole and linezolid (1-2 log(10) cfu at 72 h). CONCLUSIONS: Moxifloxacin is active against both extracellular and intracellular CA-MRSA if the MIC is low, and is more effective than clindamycin, co-trimoxazole and linezolid.
Asunto(s)
Antibacterianos/farmacología , Compuestos Aza/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Quinolinas/farmacología , Acetamidas/farmacología , Línea Celular , Clindamicina/farmacología , Infecciones Comunitarias Adquiridas/microbiología , Fluoroquinolonas , Humanos , Linezolid , Macrófagos/microbiología , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Moxifloxacino , Oxazolidinonas/farmacología , Fagocitosis , Infecciones Estafilocócicas/microbiología , Combinación Trimetoprim y Sulfametoxazol/farmacologíaRESUMEN
Synergy time-kill studies of 47 methicillin-resistant Staphylococcus aureus strains with differing resistance phenotypes showed that combinations of subinhibitory concentrations of ACHN-490 and daptomycin yielded synergy against 43/47 strains at 24 h, while the combination was indifferent against the remaining 4 strains. ACHN-490 and ceftobiprole showed synergy in 17/47 strains tested at 24 h, while 6/47 strains showed synergy for subinhibitory combinations of ACHN-490 and linezolid.
Asunto(s)
Acetamidas/farmacología , Aminoglicósidos/farmacología , Daptomicina/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Oxazolidinonas/farmacología , Sisomicina/análogos & derivados , Aminoglicósidos/química , Antibacterianos/farmacología , Cefalosporinas/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Sinergismo Farmacológico , Linezolid , Pruebas de Sensibilidad Microbiana , Sisomicina/química , Sisomicina/farmacología , Factores de TiempoRESUMEN
We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ss-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to > or =16. The MPC/MIC ratios for beta-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 microg/ml) than those for ss-lactamase-negative strains.
Asunto(s)
Antibacterianos/administración & dosificación , Carbapenémicos/administración & dosificación , Genes Bacterianos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/genética , Mutación , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/genética , Doripenem , Farmacorresistencia Bacteriana/genética , Ertapenem , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Bacterias Gramnegativas/enzimología , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Imipenem/administración & dosificación , Técnicas In Vitro , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Meropenem , Pruebas de Sensibilidad Microbiana , Fenotipo , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Tienamicinas/administración & dosificación , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , beta-Lactamas/administración & dosificaciónRESUMEN
Synergy time-kill studies against 40 methicillin-resistant Staphylococcus aureus (MRSA) strains of differing resistance phenotypes were conducted. Subinhibitory concentrations of telavancin were combined with sub-MIC concentrations of other antimicrobial agents that might be used in combination with telavancin to provide Gram-negative coverage. The highest incidence of synergy was found after 24 h with gentamicin (90% of strains), followed by ceftriaxone (88%), rifampin and meropenem (each 65%), cefepime (45%), and ciprofloxacin (38%) for combinations tested at or below the intermediate breakpoint for each agent.
Asunto(s)
Aminoglicósidos/farmacología , Antibacterianos/farmacología , Gentamicinas/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Cefepima , Ceftriaxona/farmacología , Cefalosporinas/farmacología , Ciprofloxacina/farmacología , Sinergismo Farmacológico , Lipoglucopéptidos , Meropenem , Pruebas de Sensibilidad Microbiana , Oxacilina/farmacología , Rifampin/farmacología , Tienamicinas/farmacología , Factores de TiempoRESUMEN
We tested the propensity of three quinolones to select for resistant Streptococcus pneumoniae mutants by determining the mutant prevention concentration (MPC) against 100 clinical strains, some of which harbored mutations in type II topoisomerases. Compared with levofloxacin and gemifloxacin, moxifloxacin had the lowest number of strains with MPCs above the susceptibility breakpoint (P<0.001), thus representing a lower selective pressure for proliferation of resistant mutants. Only moxifloxacin gave a 50% MPC (MPC50) value (1 microg/ml) within the susceptible range.
Asunto(s)
Antibacterianos/farmacología , Compuestos Aza/farmacología , Fluoroquinolonas/farmacología , Levofloxacino , Naftiridinas/farmacología , Ofloxacino/farmacología , Quinolinas/farmacología , Streptococcus pneumoniae/efectos de los fármacos , ADN-Topoisomerasas de Tipo II/genética , Farmacorresistencia Bacteriana/genética , Gemifloxacina , Pruebas de Sensibilidad Microbiana , Moxifloxacino , Mutación , Reacción en Cadena de la Polimerasa , Streptococcus pneumoniae/genéticaRESUMEN
CEM-101 had MIC ranges of 0.002 to 0.016 microg/ml against macrolide-susceptible pneumococci and 0.004 to 1 microg/ml against macrolide-resistant phenotypes. Only 3 strains with erm(B), with or without mef(A), had CEM-101 MICs of 1 microg/ml, and 218/221 strains had CEM-101 MICs of
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Macrólidos/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacos , Triazoles/farmacología , Pruebas de Sensibilidad Microbiana , Penicilina G/farmacologíaRESUMEN
Radezolid is a novel biaryloxazolidinone in clinical development which shows improved activity, including against linezolid-resistant strains. In a companion paper (29), we showed that radezolid accumulates about 11-fold in phagocytic cells, with approximately 60% of the drug localized in the cytosol and approximately 40% in the lysosomes of the cells. The present study examines its activity against (i) bacteria infecting human THP-1 macrophages and located in different subcellular compartments (Listeria monocytogenes, cytosol; Legionella pneumophila, vacuoles; Staphylococcus aureus and Staphylococcus epidermidis, mainly phagolysosomal), (ii) strains of S. aureus with clinically relevant mechanisms of resistance, and (iii) isogenic linezolid-susceptible and -resistant S. aureus strains infecting a series of phagocytic and nonphagocytic cells. Radezolid accumulated to similar levels ( approximately 10-fold) in all cell types (human keratinocytes, endothelial cells, bronchial epithelial cells, osteoblasts, macrophages, and rat embryo fibroblasts). At equivalent weight concentrations, radezolid proved consistently 10-fold more potent than linezolid in all these models, irrespective of the bacterial species and resistance phenotype or of the cell type infected. This results from its higher intrinsic activity and higher cellular accumulation. Time kill curves showed that radezolid's activity was more rapid than that of linezolid both in broth and in infected macrophages. These data suggest the potential interest of radezolid for recurrent or persistent infections where intracellular foci play a determinant role.
Asunto(s)
Antibacterianos/farmacología , Legionella pneumophila/efectos de los fármacos , Listeria monocytogenes/efectos de los fármacos , Oxazolidinonas/farmacología , Fagocitos/efectos de los fármacos , Fagocitos/microbiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Acetamidas/administración & dosificación , Acetamidas/farmacología , Animales , Antibacterianos/administración & dosificación , Células Cultivadas , Relación Dosis-Respuesta a Droga , Farmacorresistencia Bacteriana , Humanos , Linezolid , Pruebas de Sensibilidad Microbiana , Oxazolidinonas/administración & dosificación , RatasRESUMEN
OBJECTIVES: Increasing antibiotic resistance and interest in matching antibiotic therapy with pharmacokinetic/pharmacodynamic characteristics of isolates has led to increasing demands for determination of MICs. This can lead to increased costs for the laboratory. The spiral gradient endpoint (SGE) technique, a low-cost method of MIC determination, was developed some years ago. Although the technique showed good correlation with reference methods, it was not widely employed, mainly due to the introduction of alternative methods. We have revisited this technique and evaluated it for the determination of MICs for fastidious organisms. METHODS: The SGE method was first optimized for fastidious organisms using Haemophilus influenzae. Intra-batch and inter-batch reproducibility was determined for H. influenzae, Streptococcus pneumoniae, Moraxella catarrhalis and Neisseria gonorrhoeae. The method was then evaluated by comparison of MICs for clinical isolates of these organisms determined by SGE with those determined with the reference method. RESULTS: Optimization of the technique resulted in a method with excellent reproducibility for all organisms tested [SD 0.10-0.337; coefficient of variation (CV) 8.59%-18.66%]. These SDs/CVs were lower than those of the reference methods (0.27-2.34; 31.0%-63.8%). There was excellent correlation of the MICs with the reference methods (0.908-0.930) and insignificant differences in numbers of strains in each resistance category, with no tendency for SGE to produce higher or lower MICs than the reference method (P > 0.05). CONCLUSIONS: SGE was shown to be reproducible and produced results that correlated well with standard techniques for fastidious organisms. The method offers a rapid, flexible, cost-effective alternative for smaller laboratories and for routine use in developing countries.
Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/métodos , Bacterias/aislamiento & purificación , Infecciones Bacterianas/microbiología , Humanos , Pruebas de Sensibilidad Microbiana/economía , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
OBJECTIVES: Several methods have been introduced for detection of vancomycin-non-susceptible Staphylococcus aureus [heterogeneous vancomycin-intermediate S. aureus (hVISA) and vancomycin-intermediate S. aureus (VISA)]. However, the limitations of these methods can delay appropriate therapy for the patient. This study evaluated the spiral gradient endpoint (SGE) technique for detection of hVISA/VISA. METHODS: The SGE method was evaluated for intra-batch, inter-batch and inter-observer reproducibility in comparison with MICs determined by agar dilution. Three media, Mueller-Hinton agar, brain heart infusion agar and brain heart infusion agar with 5% glucose, were evaluated. The SGE method was compared with agar dilution for correlation of MIC and susceptibility category using control strains, clinical isolates and induced vancomycin-non-susceptible strains. RESULTS: The SGE method had good reproducibility and there was excellent correlation of MICs generated by SGE using brain heart infusion agar with those by agar dilution (r(2)â=0.950), with no difference in resistance categories generated by the two methods. All VISA isolates were correctly identified and the method allowed easy identification of hVISA by means of the trailing endpoint. CONCLUSIONS: SGE offers a simple, rapid and cost-effective alternative method for the detection of hVISA/VISA for the routine laboratory. Early recognition of vancomycin-non-susceptible strains can allow the change to appropriate antibiotics, resulting in potentially better patient outcomes.
Asunto(s)
Staphylococcus aureus/efectos de los fármacos , Resistencia a la Vancomicina , Medios de Cultivo/química , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Reproducibilidad de los ResultadosRESUMEN
Faropenem demonstrated low MICs (< or = 1 microg/ml) for all penicillin-susceptible and nonsusceptible pneumococci and exhibited very strong abilities to bind to Streptococcus pneumoniae penicillin-binding proteins (PBPs), except for PBP2X. The lower faropenem affinity for PBP2X did not affect MICs for any strains tested, and only imipenem had lower MICs, with much lower binding affinities for all PBPs tested, than faropenem.
Asunto(s)
Antibacterianos , Proteínas de Unión a las Penicilinas/metabolismo , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/metabolismo , beta-Lactamas , Antibacterianos/metabolismo , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Humanos , Pruebas de Sensibilidad Microbiana , Resistencia a las Penicilinas , Proteínas de Unión a las Penicilinas/química , Proteínas de Unión a las Penicilinas/genética , beta-Lactamas/metabolismo , beta-Lactamas/farmacologíaRESUMEN
Agar dilution MIC methodology was used to compare the activity of sulopenem with those of amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 431 anaerobes. Overall, MIC(50)/(90) values were as follows: sulopenem, 0.25/1.0 microg/ml; amoxicillin/clavulanate, 0.5/2.0 microg/ml; ampicillin/sulbactam, 0.5/4.0 microg/ml; piperacillin/tazobactam, 0.25/8.0 microg/ml; imipenem, 0.06/1.0 microg/ml; clindamycin, 0.25/16.0 microg/ml; and metronidazole, 1.0/4.0 microg/ml.
Asunto(s)
Antibacterianos/farmacología , Bacterias Anaerobias/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Lactamas/farmacología , Humanos , Lactamas/química , Pruebas de Sensibilidad Microbiana/métodos , Pruebas de Sensibilidad Microbiana/normas , Profármacos/química , Profármacos/farmacologíaRESUMEN
For 297 penicillin-susceptible, -intermediate, and -resistant pneumococcal strains, the sulopenem MIC(50)s were 0.008, 0.06, and 0.25, respectively, and the sulopenem MIC(90)s were 0.016, 0.25, and 0.5 microg/ml, respectively. The MIC(50)s of amoxicillin for the corresponding strains were 0.03, 0.25, and 2.0 microg/ml, respectively, and the MIC(90)s were 0.03, 1.0, and 8.0 microg/ml, respectively. The combination of amoxicillin and clavulanate gave MICs similar to those obtained with amoxicillin alone. The sulopenem MICs were similar to those of imipenem and meropenem. The MICs of ss-lactams increased with those of penicillin G, and among the quinolones tested, moxifloxacin had the lowest MICs. Additionally, 45 strains of drug-resistant type 19A pneumococci were tested by agar dilution and gave sulopenem MIC(50)s and MIC(90)s of 1.0 and 2.0 microg/ml, respectively. Both sulopenem and amoxicillin (with and without clavulanate) were bactericidal against all 12 strains tested at 2x MIC after 24 h. Thirty-one strains from 10 countries with various penicillin, amoxicillin, and carbapenems MICs, including those with the highest sulopenem MICs, were selected for sequencing analysis of the pbp1a, pbp2x, and pbp2b regions encoding the transpeptidase active site and MurM. We did not find any correlations between specific penicillin-binding protein-MurM patterns and changes in the MICs.