RESUMEN
Tedizolid is an oxazolidinone with an antimicrobial in vitro potency advantage against Gram-positive bacterial pathogens compared to other currently marketed drugs in this class, including linezolid. Tedizolid was compared to linezolid when tested against Staphylococcus aureus and Streptococcus pneumoniae isolates collected from countries in Latin America and the Asia-Pacific. Isolates were tested by broth microdilution susceptibility methods against tedizolid, linezolid, and non-class comparators in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. The activity of tedizolid against S. aureus was potent and consistent in Latin America (MIC90, 0.5 mg/L), Australia and New Zealand (MIC90, 0.25 mg/L), and China (MIC90, 0.5 mg/L). Based on MIC90 results, tedizolid was four- to eight-fold more active than linezolid against S. aureus, including both methicillin-susceptible and -resistant isolates. Only two tedizolid non-susceptible strains were observed; both had intermediate minimum inhibitory concentration (MIC) values of 1 mg/L, for which the MICs of linezolid was higher (≥2 mg/L). Tedizolid (MIC90, 0.25 mg/L) was four-fold more potent than linezolid (MIC90, 1 mg/L) against S. pneumoniae in all countries that provided isolates. The findings from this study support the global clinical development of tedizolid for Gram-positive infections.
Asunto(s)
Antibacterianos/farmacología , Organofosfatos/farmacología , Oxazoles/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/aislamiento & purificación , Australasia , China , Humanos , América Latina , Linezolid/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVES: Ceftaroline fosamil is indicated for the treatment of community-acquired bacterial pneumonia and ceftriaxone has an indication for lower respiratory tract infections. This study was conducted to compare the relative in vitro activities of these two agents against bacterial species associated with community-associated respiratory tract infections. METHODS: In all, 13â005 isolates of Staphylococcus aureus, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae were collected in 2012-14 from 39 countries in the Asia-Pacific region, Europe, Latin America and Africa-Middle East from respiratory tract specimens. The identification was confirmed centrally by MALDI-TOF and broth microdilution susceptibility testing and interpretation was done according to CLSI guidelines. RESULTS: Ceftaroline was 16-fold more potent against MSSA (MIC90 0.25 versus 4 mg/L) than ceftriaxone and ≥16-fold more potent against MRSA (MIC90 2 versus >32 mg/L). Ceftaroline was 16-fold more potent against S. pneumoniae (MIC90 0.12-0.25 mg/L) compared with ceftriaxone (MIC90 1-2 mg/L), with higher MIC values observed among penicillin-non-susceptible isolates for both agents. Similar activity (MIC90 ≤0.03 mg/L) was observed for ceftaroline and ceftriaxone against H. influenzae, with higher MIC values observed in the Asia-Pacific region for both agents compared with other regions. Ceftaroline was 4- to 8-fold more active against M. catarrhalis (MIC90 0.12-0.25 mg/L) compared with ceftriaxone (MIC90 1 mg/L). CONCLUSIONS: These global MIC data demonstrated that ceftaroline exhibited superior in vitro activity compared with ceftriaxone against bacterial species that commonly cause community-associated respiratory tract infections.
Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Infecciones Bacterianas/microbiología , Ceftriaxona/farmacología , Cefalosporinas/farmacología , Infecciones del Sistema Respiratorio/microbiología , Anciano , Anciano de 80 o más Años , Bacterias/clasificación , Bacterias/aislamiento & purificación , Infecciones Comunitarias Adquiridas/microbiología , Monitoreo Epidemiológico , Femenino , Salud Global , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , CeftarolinaRESUMEN
Gepotidacin inhibits bacterial DNA replication through a mode different from that of fluoroquinolones. Gepotidacin and comparators were tested by broth and agar dilution against clinical isolates. The in vitro activities of gepotidacin were comparable against methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) isolates (MIC90, 0.5 µg/ml). The gepotidacin MIC90s were as follows (in micrograms per milliliter) for the indicated bacteria: Streptococcus pyogenes, 0.25; Escherichia coli, 2; Moraxella catarrhalis, ≤ 0.06; Streptococcus pneumoniae (0.25), Haemophilus influenzae, 1; Clostridium perfringens, 0.5; and Shigella spp., 1, including levofloxacin-resistant subsets. Gepotidacin warrants further investigation for clinical development.
Asunto(s)
Acenaftenos/farmacología , Antibacterianos/farmacología , Replicación del ADN/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/farmacología , Inhibidores de Topoisomerasa II/farmacología , Clostridium perfringens/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Escherichia coli/efectos de los fármacos , Haemophilus influenzae/efectos de los fármacos , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Shigella/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacosRESUMEN
Intensive care units (ICUs) are often described as hotbeds of antimicrobial resistance, with high rates of extended-spectrum ß-lactamase (ESBL)-producing and multidrug-resistant (MDR) Enterobacteriaceae. Data from the SMART study were used to examine differences between the susceptibility of Enterobacteriaceae from ICU and non-ICU wards in Europe and North America. In total, 21,470 Enterobacteriaceae isolates from intra-abdominal and urinary tract infections were collected at 90 sites in 20 European and North American countries in 2011-2013. Susceptibility and ESBL phenotypes were determined using the CLSI broth microdilution method and breakpoints. Susceptibility was lower and ESBL and MDR rates were higher in ICUs, with much greater ICU/non-ICU differences in Europe than North America. Susceptibility was lower and ESBL and MDR rates were higher in Europe than in North America in both patient locations. Resistance among Enterobacteriaceae in Europe was largely driven by Klebsiella pneumoniae, which had high rates of ESBLs (41.2% in ICUs; mostly CTX-M) and carbapenemases (13.2%; mostly KPC and OXA). For all Enterobacteriaceae combined, only ertapenem and amikacin inhibited >90% of isolates in ICUs in both regions. In North America, ertapenem, imipenem and amikacin inhibited >90% of K. pneumoniae from ICUs, whereas in Europe only amikacin did. ESBL and MDR rates varied considerably within Europe. Antimicrobial resistance was higher in Europe than North America, especially in ICUs. Further surveillance at the country, hospital and even patient ward level, and investigation of reasons for these findings, would be useful for the development of effective strategies to reduce antimicrobial resistance in ICUs.
RESUMEN
Clinical development of CEM-102 (fusidic acid) has recently begun in the United States for chronic oral treatment of prosthetic joint infections. To support this development, the in vitro activity of fusidic acid against important Staphylococcus aureus clones and resistance phenotypes was determined. Against 51 such isolates, the modal fusidic acid MIC was 0.12 µg/ml (range, 0.06 to 0.25 µg/ml for 49 isolates). This level of in vitro fusidic acid activity underscores the potential clinical utility of this compound in the United States.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Ácido Fusídico/farmacología , Staphylococcus aureus/efectos de los fármacos , Medios de Cultivo , Pruebas de Sensibilidad Microbiana , Fenotipo , Staphylococcus aureus/crecimiento & desarrolloRESUMEN
OBJECTIVES: In multiple sclerosis (MS), contrast-enhancing lesions (CELs) in T1-weighted postcontrast MRI are considered markers of blood-brain barrier breakdown. It remains unknown if re-enhancement can be considered a radiologic indicator of different pathology in CELs. We investigated 1) the incidence of re-enhancing lesions (re-CELs) from chronic lesions; 2) differences in size, magnetization transfer ratio (MTR), and likelihood to appear as acute black holes (aBHs) between new lesions (n-CELs) and re-CELs; and 3) associations between re-CELs and features indicating more advanced disease. METHODS: In this retrospective natural history study, we examined 264 monthly MRI scans performed at month 1 (M1), month 2 (M2), and month 3 (M3) for 88 patients with MS. CELs were defined as n-CELs if not present in the M1 T2W MRI and re-CELs if present in the M1 T2W MRI. RESULTS: A total of 311 (82.7%) n-CELs and 65 (17.3%) re-CELs were identified. Of the 88 patients, 54 presented only n-CELs, 8 presented only re-CELs, and 26 presented both CEL types. Patients with both lesion types presented more CELs than those presenting only one type (p = 0.01). Re-CELs were larger (z = 2.72, p = 0.007) and had lower MTR (z = -2.80, p = 0.005) than n-CELs but the estimated proportion of aBHs from n-CELs was similar (z = -0.09, p = 0.1) from the proportion of aBHs from re-CELs. CONCLUSIONS: Nearly 20% of CELs represent the reoccurrence of enhancement in chronic plaques. Re-CELs represent larger areas of inflammation, not necessarily associated with larger areas of edema.
Asunto(s)
Encéfalo/patología , Esclerosis Múltiple/patología , Fibras Nerviosas Mielínicas/patología , Adulto , Barrera Hematoencefálica/patología , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Surveillance initiatives to track Streptococcus pneumoniae resistance trends are important for understanding the current in vitro effectiveness of available antimicrobial agents. The antimicrobial susceptibility profiles of S. pneumoniae (n=1479 isolates) collected from 17 geographical areas across the USA (2003-2004) were analysed; 36.8% of isolates were resistant to one or more agents (24.4% were multidrug-resistant, i.e. resistant to two or more antimicrobial classes). Multidrug resistance involved resistance to beta-lactams, macrolides, tetracycline and trimethoprim/sulphamethoxazole, but rarely fluoroquinolones (>96% of multidrug-resistant isolates were fluoroquinolone-susceptible). Multidrug resistance rates were prominent regardless of the geographical region surveyed. As this trend continues, the empirical therapeutic options for S. pneumoniae infections will diminish and there will be an ongoing need to evaluate the effectiveness of potent fluoroquinolones such as gemifloxacin.
Asunto(s)
Antibacterianos/farmacología , Infecciones Comunitarias Adquiridas/epidemiología , Farmacorresistencia Bacteriana Múltiple , Neumonía Neumocócica/epidemiología , Vigilancia de la Población/métodos , Streptococcus pneumoniae/efectos de los fármacos , Infecciones Comunitarias Adquiridas/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Neumonía Neumocócica/microbiología , Estados Unidos/epidemiologíaRESUMEN
We screened 313 ceftazidime-resistant Enterobacteriaceae isolates obtained in the United States from 1999 to 2004 for all three known qnr genes. A qnr gene was present in 20% of Klebsiella pneumoniae isolates, 31% of Enterobacter sp. isolates, and 4% of Escherichia coli isolates. qnrA and qnrB occurred with equivalent frequencies and, except for qnrB in enterobacters, were stable over time. qnrS was absent.
Asunto(s)
Antibacterianos/farmacología , Ceftazidima/farmacología , Infecciones por Enterobacteriaceae/microbiología , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/aislamiento & purificación , Genes Bacterianos , Prevalencia , Distribución por Edad , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Farmacorresistencia Bacteriana Múltiple/genética , Enterobacteriaceae/genética , Infecciones por Enterobacteriaceae/epidemiología , Escherichia coli , Femenino , Humanos , Pacientes Internos , Klebsiella pneumoniae , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Datos de Secuencia Molecular , Estudios Retrospectivos , Salmonella enterica/clasificación , Salmonella enterica/genética , Homología de Secuencia de Aminoácido , Estados Unidos/epidemiologíaRESUMEN
The plasmid-encoded quinolone resistance gene qnrA confers low-level quinolone resistance, facilitating selection of higher-level resistance. Epidemiologic surveys for qnrA were extended to isolates of Enterobacter spp. and to quinolone-susceptible Enterobacteriaceae. Two (10%) of 20 ceftazidime-resistant quinolone-susceptible Klebsiella pneumoniae strains carried the gene, as did 12 (17%) of 71 ceftazidime-resistant Enterobacter strains from across the United States. One of these Enterobacter isolates was quinolone susceptible. Thus, qnrA is present in quinolone-resistant and quinolone-susceptible Enterobacter and Klebsiella strains in the United States.
Asunto(s)
Antiinfecciosos/farmacología , Farmacorresistencia Bacteriana/genética , Infecciones por Enterobacteriaceae/epidemiología , Enterobacteriaceae/efectos de los fármacos , Plásmidos/genética , Quinolonas/farmacología , Proteínas Bacterianas/genética , Enterobacter cloacae/efectos de los fármacos , Enterobacter cloacae/genética , Enterobacteriaceae/genética , Infecciones por Enterobacteriaceae/microbiología , Humanos , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Estados Unidos/epidemiologíaRESUMEN
The GLOBAL (Global Landscape On Bactericidal Activity of Levofloxacin) Surveillance programme monitored antimicrobial susceptibility patterns of the key respiratory tract pathogens Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis collected in Brazil during 1997-1998, 1999-2000 and 2001-2002. Penicillin and azithromycin resistance among S. pneumoniae strains increased from 1997-1998, reaching 7.9% and 9.5%, respectively, in 2001-2002. Although decreasing by 4.9% since the previous study, trimethoprim-sulphamethoxazole resistance remained high at 33.7%. Concurrent resistance to penicillin, azithromycin and trimethoprim-sulphamethoxazole was seen in 2.9% of the S. pneumoniae isolates collected. Levofloxacin remained extremely active against S. pneumoniae, with 0.3% resistance reported in 1997-1998 and 0% resistance in 1999-2000 and 2001-2002. beta-Lactamase production in H. influenzae was > 10% in all three studies, with correspondingly high rates of ampicillin resistance. Trimethoprim-sulphamethoxazole was the least active agent tested against H. influenzae, with resistance rates of > 40% recorded in all three studies. All H. influenzae isolates were susceptible to cefuroxime, ceftriaxone, azithromycin and levofloxacin. Of the M. catarrhalis isolates, 98.0% in 1997-1998, 98.0% in 1999-2000 and 81.8% in 2001-2002 were beta-lactamase-positive. The continued high prevalence of antimicrobial resistance in Brazil underscores the importance of current surveillance initiatives. Levofloxacin, a fluoroquinolone prescribed widely for respiratory tract infections, continued to show potent activity against key respiratory pathogens.
Asunto(s)
Antibacterianos/farmacología , Haemophilus influenzae/efectos de los fármacos , Levofloxacino , Moraxella catarrhalis/efectos de los fármacos , Ofloxacino/farmacología , Vigilancia de la Población , Infecciones del Sistema Respiratorio/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Brasil , Farmacorresistencia Bacteriana , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Antimicrobial resistance patterns among the principal bacterial pathogens from infections of the respiratory tract, blood, skin and soft tissue, and urinary tract of pediatric patients from the USA, Canada, Germany, France, and Italy were studied using the The Surveillance Network (TSN) database. Among Streptococcus pneumoniae isolates from respiratory tract infections, the prevalence of high-level penicillin resistance (MIC>/=2 microg/ml) ranged from 1.1 (Italy) to 36.2% (USA); erythromycin resistance was higher, ranging from 13.4 (Germany) to 63.8% (France). The prevalence of beta-lactamase-positive Haemophilus influenzae among isolates from lower respiratory tract infections ranged from <10 (Italy and Germany) to 38.4% (USA). Among isolates from blood and skin and soft tissue infections, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) ranged from 7.2% (Canada and Germany) to 27.3% (Italy). The prevalence of Escherichia coli and Klebsiella pneumoniae with putative extended-spectrum beta-lactamases among isolates from blood, urinary tract, and skin and soft tissue infections ranged from 0 (Germany and France) to 29.6% (Italy). With the exception of pseudomonal infections or infections with MRSA, amoxicillin-clavulanate retained moderate activity, whilst ceftriaxone and cefepime were the most effective broad-spectrum injectable agents. Meropenem was the most effective agent against Pseudomonas aeruginosa with <5% resistance. Low levels of resistance, along with acceptable safety profiles and the availability of convenient oral formulations, continue to support the use of ceftriaxone, cefepime, amoxicillin-clavulanate, and meropenem as viable options for the treatment of infections in pediatric patients.
Asunto(s)
Antibacterianos/farmacología , Bacteriemia/microbiología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Bacteriemia/epidemiología , Canadá/epidemiología , Niño , Preescolar , Farmacorresistencia Bacteriana , Femenino , Francia/epidemiología , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Humanos , Incidencia , Lactante , Italia/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Estudios Multicéntricos como Asunto , Sistema de Registros , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Enfermedades Cutáneas Bacterianas/epidemiología , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones de los Tejidos Blandos/epidemiología , Infecciones de los Tejidos Blandos/microbiología , Estados Unidos/epidemiología , Infecciones Urinarias/epidemiología , Infecciones Urinarias/microbiologíaRESUMEN
OBJECTIVE: The authors studied the susceptibility of 1,647 non-repeat isolates of Escherichia coli to quinolones and fluoroquinolones. METHOD: The strains were isolated from non-complicated urinary infections in women 18-64 years of age. Data was provided by the TSN Database France, a real time electronic database which collects antibiotic susceptibility results and patient demographic data. The data was collected from 1999 to 2001 in 63 French hospital laboratories, each using their own routine test methods. Quantitative data was interpreted (S, I, R) according to CA-SFM breakpoint guidelines. RESULTS: Ninety-eight and 94,6 % of the strains were susceptible to ciprofloxacin and nalidixic acid respectively. Cross resistance was assessed as well as intrinsic difference in activity within the fluoroquinolone class. Current fluoroquinolones are still highly efficient, and ciprofloxacin is the most active. CONCLUSION: Since 1996, little change in resistance to fluoroquinolones has been observed. These results confirm the choice of fluoroquinolones as first intention therapy as recommended by consensus conferences.
Asunto(s)
Antiinfecciosos/farmacología , Infecciones por Escherichia coli/tratamiento farmacológico , Escherichia coli/efectos de los fármacos , Fluoroquinolonas/farmacología , Ácido Nalidíxico/farmacología , Infecciones Urinarias/tratamiento farmacológico , Adolescente , Adulto , Farmacorresistencia Microbiana , Escherichia coli/aislamiento & purificación , Escherichia coli/patogenicidad , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Bacillus anthracis is a bacterial species that could be used in a bioterrorist attack. We tested a collection of isolates with a range of relevant antimicrobial compounds. All isolates tested were susceptible to ciprofloxacin and doxycycline. Penicillin and amoxicillin, with or without clavulanate, showed in vitro activity against all B. anthracis isolates. Ceftriaxone demonstrated lower-level in vitro activity compared to penicillin-related compounds against B. anthracis. In vitro data from this study are in keeping with available guidelines.
Asunto(s)
Antibacterianos/farmacología , Bacillus anthracis/efectos de los fármacos , Bioterrorismo , Ciprofloxacina/farmacología , Carbunco/microbiología , Bacillus anthracis/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Esporas Bacterianas/metabolismoRESUMEN
OBJECTIVE: To assess the current (2001) activity of respiratory fluoroquinolones and comparator agents against respiratory pathogens isolated in European countries. METHODS: During 2000-2001, we prospectively collected 1995 isolates of Haemophilus influenzae, 1870 isolates of Streptococcus pneumoniae and 649 isolates of Moraxella catarrhalis from hospital laboratories in France, Germany, Greece, Italy, Spain and the UK. National Committee for Clinical Laboratory Standards (NCCLS)-approved broth microdilution antimicrobial susceptibility testing methods and interpretive criteria were used throughout. RESULTS: Of the S. pneumoniae isolates, 99.6% were susceptible to moxifloxacin, gatifloxacin and levofloxacin; the corresponding figure for H. influenzae was 100%. All M. catarrhalis isolates had moxifloxacin MICs = 0.12 mg/L. For all three pathogens, fluoroquinolone susceptibility remained unchanged from the previous 1997-98 study. The incidence of penicillin non-susceptibility in the S. pneumoniae isolates tested remained similar to or higher than that recorded in previous studies: France, 165/291 (56.7%); Germany, 46/506 (9.1%); Greece, 20/55 (36.4%); Italy, 45/364 (12.4%); Spain, 146/268 (54.5%); and the UK, 26/386 (6.7%). Significant levels of resistance to oral compounds (cefuroxime, cefaclor, cefdinir, clarithromycin, azithromycin, tetracycline, and trimethoprim-sulfamethoxazole) were detected among S. pneumoniae isolates. beta-Lactamase production among H. influenzae isolates ranged from 6.2% to 33.1% per country, and ampicillin, clarithromycin or trimethoprim-sulfamethoxazole resistance were the most common phenotypes detected. beta-Lactamase production among M. catarrhalis isolates ranged from 94.1% to 100% per country. CONCLUSIONS: With the exception of a few localized reports, resistance to moxifloxacin and other new fluoroquinolones in common respiratory pathogens is a rare occurrence, despite significant resistance to other compound classes. Surveillance will play a key role in tracking changes in fluoroquinolone susceptibility in European countries.
Asunto(s)
Antiinfecciosos/farmacología , Compuestos Aza , Fluoroquinolonas , Haemophilus influenzae/efectos de los fármacos , Moraxella catarrhalis/efectos de los fármacos , Quinolinas , Streptococcus pneumoniae/efectos de los fármacos , Farmacorresistencia Bacteriana/fisiología , Moxifloxacino , Estudios RetrospectivosRESUMEN
In 2000-2001, 840 clinical isolates of Haemophilus influenzae were collected from laboratories in France, Germany, Italy and Spain (210 isolates/country). Beta-Lactamase production among the isolates varied considerably by country, ranging from 8.1% in Germany to 34.8% in France. H. influenzae from patients
Asunto(s)
Antibacterianos/farmacología , Haemophilus influenzae/efectos de los fármacos , Europa (Continente)/epidemiología , Infecciones por Haemophilus/diagnóstico , Haemophilus influenzae/enzimología , Haemophilus influenzae/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos , beta-Lactamasas/biosíntesisRESUMEN
OBJECTIVE: To assess the activities of levofloxacin and the comparator agents erythromycin, clarithromycin, azithromycin and doxycycline against atypical respiratory pathogens. METHODS: One hundred and forty-six Legionella pneumophila, 41 Mycoplasma pneumoniae and nine Chlamydia pneumoniae isolates were procured from various culture collections in North America and Europe and tested for susceptibility to the above agents by broth microdilution. The isolates came primarily from clinical sources and were collected from patients between 1995 and 1999. RESULTS: Against L. pneumophila, levofloxacin was the most active agent, with an MIC(90) of 0.03 mg/L, twofold more active than clarithromycin (0.06 mg/L), 16-fold more active than erythromycin and azithromycin (0.5 mg/L) and 64-fold more active than doxycycline. Against M. pneumoniae, azithromycin (MIC(90) < or = 0.0005 mg/L) was the most active agent. However, two isolates of M. pneumoniae, one from the USA and one from Finland, were macrolide resistant (MIC > or = 4 mg/L), but levofloxacin susceptible (MIC 0.25 mg/L). The geographic origin of L. pneumophila and M. pneumoniae did not affect the MIC range for any antimicrobial agent tested. Against C. pneumoniae, clarithromycin was the most active agent, with an MIC range of < or =0.008-0.03 mg/L. CONCLUSIONS: Levofloxacin had comparable activity to the other agents tested against the atypical respiratory pathogens, confirming its potential as an alternative for empirical therapy of community-acquired pneumonia.
Asunto(s)
Antiinfecciosos/farmacología , Chlamydophila pneumoniae/efectos de los fármacos , Farmacorresistencia Bacteriana , Legionella pneumophila/efectos de los fármacos , Levofloxacino , Mycoplasma pneumoniae/efectos de los fármacos , Ofloxacino/farmacología , Antibacterianos/farmacología , Chlamydophila pneumoniae/fisiología , Doxiciclina/farmacología , Europa (Continente) , Humanos , Legionella pneumophila/fisiología , Macrólidos , Pruebas de Sensibilidad Microbiana , Mycoplasma pneumoniae/fisiología , América del NorteRESUMEN
A multi-center surveillance study was conducted in Thailand during 1999-2000 to determine antimicrobial susceptibilities among the respiratory pathogens Streptococcus pneumoniae (n = 206), Haemophilus influenzae (n = 305), and Moraxella catarrhalis (n = 39). Of the S. pneumoniae isolates collected, 33.5% were penicillin-susceptible, 27.2% intermediate and 39.3% resistant. Expectedly, resistance rates to beta-lactams were higher among penicillin-resistant (ceftriaxone, 14.8%; amoxicillin-clavulanate, 42.0%; cefuroxime, 100%) than penicillin-susceptible (ceftriaxone, 0%; amoxicillin-clavulanate, 0%; cefuroxime, 0%) isolates. Likewise, azithromycin and clarithromycin resistances were 4.3% and 5.8% among penicillin-susceptible isolates, and 77.8% and 95.1% among penicillin-resistant isolates. All S. pneumoniae remained susceptible to vancomycin and 99.5% were susceptible to levofloxacin. Multidrug resistance (resistance to >3 antimicrobial classes) was present in 25.2% of pneumococcal isolates (n = 52), with resistance to azithromycin, penicillin and trimethoprim-sulfamethoxazole the most common phenotype (40/52 isolates; 77.0%). Among the isolates of H. influenzae, the prevalence of beta-lactamase production was 45.2%. All isolates of H. influenzae were susceptible to amoxicillin-clavulanate, azithromycin, ceftriaxone, cefuroxime and levofloxacin while 49.5% were resistant to trimethoprim-sulfamethoxazole. All 39 isolates of M. catarrhalis produced beta-lactamase. Azithromycin (MIC90, < or = 0.03 microg/ml) and levofloxacin (MIC90, 0.03 microg/ml) were the most active agents tested against M. catarrhalis. The results of this study may serve as a baseline for future studies to monitor antimicrobial susceptibilities among respiratory pathogens in Thailand.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Haemophilus influenzae/efectos de los fármacos , Moraxella catarrhalis/efectos de los fármacos , Infecciones del Sistema Respiratorio/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Haemophilus influenzae/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/aislamiento & purificación , Vigilancia de la Población , Streptococcus pneumoniae/aislamiento & purificación , Tailandia/epidemiologíaRESUMEN
Ceftriaxone was introduced into clinical practice in the USA in 1985 and was the first extended-spectrum (third-generation) cephalosporin approved for once-daily treatment of patients with Gram-positive or Gram-negative infections. Review of ceftriaxone activity is important given its continued use since the mid-1980s and reports of emerging resistance among all antimicrobial agent classes. We reviewed the activity of ceftriaxone and relevant comparative agents against five Gram-positive and 11 Gram-negative species for a 5-year period, 1996-2000, using data from The Surveillance Network (TSN) Database-USA. All MIC results were interpreted using NCCLS breakpoint criteria. Ceftriaxone resistance among isolates of Streptococcus pneumoniae (n=17219) remained essentially unchanged over the 5 years studied and in fact was lower from 1998 to 2000 (5.0-5.1%) than in 1996 (6.3%) and 1997 (6.6%). Ceftriaxone resistance (range, 5.1-6.9%) among viridans group streptococci (n=6621) varied by <2% from 1997 to 2000. Beta-lactam-resistant Streptococcus pyogenes (n=935) and group B beta-haemolytic streptococci (n=2267) were not identified in any year. Among methicillin-susceptible Staphylococcus aureus (n=39 284) ceftriaxone resistance was 0.1-0.3% per year from 1996 to 2000. Ceftriaxone resistance among Escherichia coli (n=472407; range, 0.2-0.4%), Klebsiella oxytoca (n=16231; range, 3.5-4.8%), Klebsiella pneumoniae (n=117754; range, 1.9-2.6%), Proteus mirabilis (n=67692; range, 0.2-0.3%), Morganella morganii (n=11251; range, 0.3-2.1%) and Serratia marcescens (n=26519; range, 1.6-3.8%) was low and consistent from 1996 to 2000. Resistance to ceftriaxone among Enterobacter cloacae (n=48114; range, 21.7-23.9%) was relatively high, compared with other Enterobacteriaceae, but unchanged from 1996 to 2000. Rates of resistance to ceftriaxone among Acinetobacter spp. (n=20813) increased from 24.8% in 1996 to 45.1% in 2000. All Haemophilus influenzae (n=7911) and Neisseria gonorrhoeae (n=218) were susceptible to ceftriaxone, as were 99.7% of Moraxella catarrhalis (n=312) tested in 1996 and 1997. In summary, ceftriaxone has retained its potent activity against the most commonly encountered Gram-positive and Gram-negative human pathogens despite widespread and ongoing clinical use for more than 15 years.
Asunto(s)
Antibacterianos/farmacología , Ceftriaxona/farmacología , Bases de Datos Factuales , Farmacorresistencia Bacteriana , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Vigilancia de la Población , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To assess the ability of 59 clinical microbiology laboratories distributed throughout Italy to correctly identify and detect reduced susceptibility to glycopeptides in staphylococci and VanA-, VanB- or VanC-mediated glycopeptide resistance in enterococci. METHODS: Eight test strains comprising three staphylococci (S. aureus ATCC 29212 and two vancomycin-intermediate S. haemolyticus [11105301, 10030683Y]) and five enterococci (E. faecalis ATCC 29212, E. faecalis ATCC 51299 VanB, E. faecium AIB40 VanA, E. faecalis V583 VanB and E. gallinarum AIB39 VanC1) were distributed to 59 Italian clinical microbiology laboratories. Each isolate was blind-coded, and laboratories were instructed to identify the strains and test isolates for susceptibility to teicoplanin and vancomycin using their standard methods. Results were assessed against consensus test results obtained by a reference laboratory. In addition, to complement data interpretation, laboratories were asked to provide retrospective routine test results from their respective hospitals. RESULTS: All 59 laboratories participating in the study completed the susceptibility testing and provided data for analysis. A total of 53 laboratories provided retrospective routine data. Overall, laboratories were able to identify isolates to the genus level successfully. E. gallinarum and S. haemolyticus posed problems for species identification, with only 40.6 and 71.2%, respectively, of results reported correctly; most incorrect results were reported as 'other species'. For enterococcal test strains, VanA phenotypes were detected correctly by 96.6% of laboratories; VanB by 30.5% (E. faecalis ATCC 51299) and 88.1% (E. faecalis V583); and VanC1 by 67.8%. For staphylococcal test strains, 28.8% (S. haemolyticus 11105301) and 23.7% (S. haemolyticus 10030683Y) of the laboratories were able to detect reduced susceptibility to vancomycin. Errors in detecting vancomycin resistance in VanB and VanC1 enterococci were made with all methods, most noticeably by disk diffusion users. For staphylococci, most errors in reporting vancomycin-intermediate resistance occurred with disk diffusion and Vitek (software version 5.04) users. Overall, considerably fewer errors occurred with the detection of teicoplanin resistance, especially for staphylococci. For 1999, routine results show that 41/1749 (2.4%) of E. faecium, 220/11 180 (2.0%) of E. faecalis, 29/24 927 (0.12%) of S. aureus and 54/22 102 (0.24%) of coagulase-negative staphylococci were reported as resistant to vancomycin. CONCLUSION: Italian laboratories are able to identify staphylococci and enterococci adequately, although all methodologies used have problems in identifying E. gallinarum and coagulase-negative staphylococci to the species level. While VanA phenotypes were efficiently detected, problems were experienced in detecting VanB and VanC phenotypes. The majority of laboratories were unable to detect reduced vancomycin susceptibility in staphylococci adequately, especially with disk diffusion and older Vitek systems. Teicoplanin appeared useful as a marker for detecting vancomycin resistance, particularly with disk diffusion. Should enterococcal VanB or staphylococcal glycopeptide-intermediate phenotypes become prevalent in Italy, it is likely that they would be under-detected. New systems under development, such as Vitek2, should improve this situation.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Enterococcus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/normas , Staphylococcus/efectos de los fármacos , Difusión , Enterococcus/clasificación , Enterococcus/aislamiento & purificación , Hospitales , Italia , Control de Calidad , Sensibilidad y Especificidad , Staphylococcus/clasificación , Staphylococcus/aislamiento & purificación , Teicoplanina/farmacología , Vancomicina/farmacología , Resistencia a la VancomicinaRESUMEN
We characterized baseline and repopulating stool isolates recovered during a phase II trial of ramoplanin for the treatment of patients with stool carriage of vancomycin-resistant enterococci (VRE). Repopulation with a strain with a related genotype was found in 74, 60, and 53% of individuals in groups treated with placebo, 100 mg of ramoplanin, and 400 mg of ramoplanin, respectively. All ramoplanin-treated patients with a culture positive for VRE at day 7 had a relapse caused by a genotypically related isolate. In ramoplanin-treated patients, antibiotics with activities against anaerobic organisms were associated with positive cultures on day 7 (relative risk [RR] = 8.8; P = 0.004), and the avoidance of such antibiotics was significantly associated with culture negativity through day 21 (RR = 0.16; P = 0.02).