Killing kinetics of four fluoroquinolones against Staphylococcus species were determined during t... more Killing kinetics of four fluoroquinolones against Staphylococcus species were determined during the first 5 h of incubation in the presence of drug concentrations ranging from the MIC to 1,024 micrograms/ml. Additionally, the relationship between killing rate and drug concentration was established. Sparfloxacin and temafloxacin were the most active quinolones assayed with greater lethal rates than ciprofloxacin and norfloxacin. The relation was biphasic with a decrease of at least 1 log10 c.f.u./ml at high drug concentrations with respect to that obtained at the optimal bactericidal concentration for all quinolone-microorganism combinations tested.
Ciprofloxacin and norfloxacin exhibited mechanism A (requires cell division as well as bacterial ... more Ciprofloxacin and norfloxacin exhibited mechanism A (requires cell division as well as bacterial protein and RNA synthesis to kill bacteria) and C (active against nondividing bacteria but requires protein and RNA synthesis) against the reference strain Staphylococcus aureus ATCC 25923, yet only mechanism A was exhibited by these fluoroquinolones when tested against three clinical isolates: S. aureus Sa-215, Staphylococcus epidermidis Se-81 and Staphylococcus haemolyticus Sx-1. On the contrary, fleroxacin exerted mechanism A and C against the three clinical isolates but only mechanism A against the reference strain. Ofloxacin displayed mechanism A against S. epidermidis Se-81, mechanism A and C against S. haemolyticus and mechanism A and B (active against nondividing bacteria and does not require protein and RNA synthesis) against the two S. aureus tested. Sparfloxacin showed mechanism A and C against the four Staphylococcus species studied, and temafloxacin was the only fluoroquinolone tested that exhibited mechanism A and B against the four bacterial strains assayed. No correlation was found between the in vitro bactericidal activity (expressed as minimum inhibitory concentration and optimal bactericidal concentration) and the mechanisms of action exhibited by these fluoroquinolones.
The high morbidity, mortality, and health care costs associated with invasive fungal infections, ... more The high morbidity, mortality, and health care costs associated with invasive fungal infections, especially in the critical care setting and immunocompromised host, have made it an excellent target for prophylactic, empiric, and preemptive therapy interventions principally based on early identification of risk factors. Early diagnosis and treatment are associated with a better prognosis. In the last years there have been important developments in antifungal pharmacotherapy. An approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the use new antifungal agents and its application in different clinical situations has been made. Furthermore, an attempt of developing a state of the art in each clinical scenario (critically ill, hematological, and solid organ transplant patients) has been performed, trying to choose the best strategy for each clinical situation (prophylaxis, pre-emptive, empirical, or targeted therapy). The high mortality rates in these settings make mandatory the application of early de-escalation therapy in critically ill patients with fungal infection. In addition, the possibility of antifungal combination therapy might be considered in solid organ transplant and hematological patients.
Major burn patients have characteristics that make them especially susceptible to candidemia, but... more Major burn patients have characteristics that make them especially susceptible to candidemia, but few studies focused on this have been published. The objectives were to evaluate the epidemiological, microbiological and clinical aspects of candidemia in major burn patients, determining factors associated with a poorer prognosis and mortality. We conducted a retrospective observational study of candidemia between 1996 and 2012 in major burn patients admitted to the La Fe University Hospital, Valencia, Spain. The study included 36 episodes of candidemia in the same number of patients, 55.6% men, mean age 37.33 years and low associated comorbidity. The incidence of candidemia varied between 0.26 and 6.09 episodes/1000 days stay in the different years studied. Candida albicans was the most common species (61.1%) followed by Candida parapsilosis (27.8%). Candidemia by C. krusei, C. glabrata or C. tropicalis were all identified after 2004. Central vascular catheter (CVC) was established as a potential source of candidemia in 36.1%, followed by skin and soft tissues of thermal injury (22.2%) and urinary tract (8.3%). Fluconazole was used in 19 patients (52.7%) and its in vitro resistance rate was 13.9%. The overall mortality was 47.2%, and mortality related to candidemia was 30.6%. Factors associated with increased mortality were those related to severe infection and shock. CVC was the most usual focus of candidemia. Fluconazole was the most common antifungal drug administered. The management of candidemia in major burn patients is still a challenge.
Enfermedades Infecciosas Y Microbiologia Clinica, Mar 14, 2013
Invasive fungal infections (IFIs) are difficult to diagnose and cause a high mortality to an expa... more Invasive fungal infections (IFIs) are difficult to diagnose and cause a high mortality to an expanding spectrum of patients. Culture of clinical samples has limitations for the diagnosis of IFI and alternative procedures have been developed. Among them, serum determination of galactomannan or beta-1,3-d-glucan, and antimicelium and antimannan antibodies are relevant. The use of molecular procedures and mass spectrometry (MALDI-TOF) are encouraging tools for the optimization of the diagnosis and management of patients with IFI. The proposal of species-specific breakpoint to classify the isolates as resistant or susceptible to antifungal agents and the necessity of monitor the azole serum levels deserve greater attention.
... Además, el método M27-A2 tiene el inconveniente de que no detecta las cepas resisten-tes a la... more ... Además, el método M27-A2 tiene el inconveniente de que no detecta las cepas resisten-tes a la amfotericina B (1), uno de los antifúngicos más uti-lizados en la práctica clínica y de los pocos que se pueden combinar. ... 18. Kontoyiannis, DP, Lewis, RE, Sagar, N. y cols. ...
The intraphagocytic killing of Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, and... more The intraphagocytic killing of Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, and Salmonella typhi by ciprofloxacin (0.1, 1 and 5 microg/ml) within human neutrophils with intact and impaired (by phenylbutazone treatment) O2-dependent killing mechanisms was studied and compared with the extracellular killing in the same medium of the intraphagocytic killing, but omitting neutrophils. The MIC/MBC of ciprofloxacin in vitro (assays performed according to NCCLS specifications) were: 0.015/0.06 for E. coli, 0.12/32 for S. marcescens, 1/16 for P. aeruginosa, and 0.007/0.06 for S. typhi. Ciprofloxacin showed bactericidal activity both extracellular and within phenylbutazone-treated and untreated neutrophils. The minimum concentration of ciprofloxacin to kill 90% of phagocytosed bacteria within neutrophils with normal O2-dependent killing power after 30 min was: 0.1 microg/ml for E. coli, and S. typhi, 1 microg/ml for P. aeruginosa, and 5 microg/ml for S. marcescens. In contrast, exposure for 60 min was required to reach this percentage within phenylbutazone treated neutrophils. The minimum concentration to kill 90% of extracellular bacteria after 30 min was: 0.1 microg/ml for E. coli, P. aeruginosa and S. typhi, and 5 microg/ml, for S. marcescens. A positive interaction between ciprofloxacin and the O2-dependent mechanisms of phagocytes was found. The reactive oxygen metabolites produced in the respiratory burst did not affect the intraphagocytic activity of ciprofloxacin. Phenylbutazone treatment of phagocytes would be a good experimental model to study the intraphagocytic killing of drugs in situations such as AIDS and chronic granulomatous disease where inefficient oxidative mechanisms of neutrophils exist.
Levels of penicillin both in blood and CSF are determined in 11 children with meningococcal menin... more Levels of penicillin both in blood and CSF are determined in 11 children with meningococcal meningitis. Authors compare these values with MIC. The therapeutic pattern was 500.000 Ul/Kg/day of benzylpenicillin, in six doses, with a single initial doses of 200.000 Ul/Kg. The results recommend not to use a lower doses in order to assure a permanently efficient penicillin concentration.
Revista espanola de quimioterapia: publicacion oficial de la Sociedad Espanola de Quimioterapia
The post antibiotic effect (PAE) of 8 strains of Pseudomonas aeruginosa with different susceptibi... more The post antibiotic effect (PAE) of 8 strains of Pseudomonas aeruginosa with different susceptibility to sparfloxacin and ciprofloxacin was evaluated by the colony counting method using centrifugation to remove the antibiotic. The bacteria were exposed for 60 min to a quinolone concentration of 1 mg/ml. The MIC of sparfloxacin and ciprofloxacin ranged from 0.25-256 mg/ml and from 0. 25-128 mg/ml, respectively. PAE values ranged from 46 8.71 to 59.6 2.51 min and from 46.33 15.2 to 62.6 3.70 min, respectively. No significant statistical differences were found in the PAE duration for quinolones nor between strains. No correlation could be established between PAE and susceptibility of P. aeruginosa to quinolones.
Killing kinetics of four fluoroquinolones against Staphylococcus species were determined during t... more Killing kinetics of four fluoroquinolones against Staphylococcus species were determined during the first 5 h of incubation in the presence of drug concentrations ranging from the MIC to 1,024 micrograms/ml. Additionally, the relationship between killing rate and drug concentration was established. Sparfloxacin and temafloxacin were the most active quinolones assayed with greater lethal rates than ciprofloxacin and norfloxacin. The relation was biphasic with a decrease of at least 1 log10 c.f.u./ml at high drug concentrations with respect to that obtained at the optimal bactericidal concentration for all quinolone-microorganism combinations tested.
Ciprofloxacin and norfloxacin exhibited mechanism A (requires cell division as well as bacterial ... more Ciprofloxacin and norfloxacin exhibited mechanism A (requires cell division as well as bacterial protein and RNA synthesis to kill bacteria) and C (active against nondividing bacteria but requires protein and RNA synthesis) against the reference strain Staphylococcus aureus ATCC 25923, yet only mechanism A was exhibited by these fluoroquinolones when tested against three clinical isolates: S. aureus Sa-215, Staphylococcus epidermidis Se-81 and Staphylococcus haemolyticus Sx-1. On the contrary, fleroxacin exerted mechanism A and C against the three clinical isolates but only mechanism A against the reference strain. Ofloxacin displayed mechanism A against S. epidermidis Se-81, mechanism A and C against S. haemolyticus and mechanism A and B (active against nondividing bacteria and does not require protein and RNA synthesis) against the two S. aureus tested. Sparfloxacin showed mechanism A and C against the four Staphylococcus species studied, and temafloxacin was the only fluoroquinolone tested that exhibited mechanism A and B against the four bacterial strains assayed. No correlation was found between the in vitro bactericidal activity (expressed as minimum inhibitory concentration and optimal bactericidal concentration) and the mechanisms of action exhibited by these fluoroquinolones.
The high morbidity, mortality, and health care costs associated with invasive fungal infections, ... more The high morbidity, mortality, and health care costs associated with invasive fungal infections, especially in the critical care setting and immunocompromised host, have made it an excellent target for prophylactic, empiric, and preemptive therapy interventions principally based on early identification of risk factors. Early diagnosis and treatment are associated with a better prognosis. In the last years there have been important developments in antifungal pharmacotherapy. An approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the use new antifungal agents and its application in different clinical situations has been made. Furthermore, an attempt of developing a state of the art in each clinical scenario (critically ill, hematological, and solid organ transplant patients) has been performed, trying to choose the best strategy for each clinical situation (prophylaxis, pre-emptive, empirical, or targeted therapy). The high mortality rates in these settings make mandatory the application of early de-escalation therapy in critically ill patients with fungal infection. In addition, the possibility of antifungal combination therapy might be considered in solid organ transplant and hematological patients.
Major burn patients have characteristics that make them especially susceptible to candidemia, but... more Major burn patients have characteristics that make them especially susceptible to candidemia, but few studies focused on this have been published. The objectives were to evaluate the epidemiological, microbiological and clinical aspects of candidemia in major burn patients, determining factors associated with a poorer prognosis and mortality. We conducted a retrospective observational study of candidemia between 1996 and 2012 in major burn patients admitted to the La Fe University Hospital, Valencia, Spain. The study included 36 episodes of candidemia in the same number of patients, 55.6% men, mean age 37.33 years and low associated comorbidity. The incidence of candidemia varied between 0.26 and 6.09 episodes/1000 days stay in the different years studied. Candida albicans was the most common species (61.1%) followed by Candida parapsilosis (27.8%). Candidemia by C. krusei, C. glabrata or C. tropicalis were all identified after 2004. Central vascular catheter (CVC) was established as a potential source of candidemia in 36.1%, followed by skin and soft tissues of thermal injury (22.2%) and urinary tract (8.3%). Fluconazole was used in 19 patients (52.7%) and its in vitro resistance rate was 13.9%. The overall mortality was 47.2%, and mortality related to candidemia was 30.6%. Factors associated with increased mortality were those related to severe infection and shock. CVC was the most usual focus of candidemia. Fluconazole was the most common antifungal drug administered. The management of candidemia in major burn patients is still a challenge.
Enfermedades Infecciosas Y Microbiologia Clinica, Mar 14, 2013
Invasive fungal infections (IFIs) are difficult to diagnose and cause a high mortality to an expa... more Invasive fungal infections (IFIs) are difficult to diagnose and cause a high mortality to an expanding spectrum of patients. Culture of clinical samples has limitations for the diagnosis of IFI and alternative procedures have been developed. Among them, serum determination of galactomannan or beta-1,3-d-glucan, and antimicelium and antimannan antibodies are relevant. The use of molecular procedures and mass spectrometry (MALDI-TOF) are encouraging tools for the optimization of the diagnosis and management of patients with IFI. The proposal of species-specific breakpoint to classify the isolates as resistant or susceptible to antifungal agents and the necessity of monitor the azole serum levels deserve greater attention.
... Además, el método M27-A2 tiene el inconveniente de que no detecta las cepas resisten-tes a la... more ... Además, el método M27-A2 tiene el inconveniente de que no detecta las cepas resisten-tes a la amfotericina B (1), uno de los antifúngicos más uti-lizados en la práctica clínica y de los pocos que se pueden combinar. ... 18. Kontoyiannis, DP, Lewis, RE, Sagar, N. y cols. ...
The intraphagocytic killing of Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, and... more The intraphagocytic killing of Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, and Salmonella typhi by ciprofloxacin (0.1, 1 and 5 microg/ml) within human neutrophils with intact and impaired (by phenylbutazone treatment) O2-dependent killing mechanisms was studied and compared with the extracellular killing in the same medium of the intraphagocytic killing, but omitting neutrophils. The MIC/MBC of ciprofloxacin in vitro (assays performed according to NCCLS specifications) were: 0.015/0.06 for E. coli, 0.12/32 for S. marcescens, 1/16 for P. aeruginosa, and 0.007/0.06 for S. typhi. Ciprofloxacin showed bactericidal activity both extracellular and within phenylbutazone-treated and untreated neutrophils. The minimum concentration of ciprofloxacin to kill 90% of phagocytosed bacteria within neutrophils with normal O2-dependent killing power after 30 min was: 0.1 microg/ml for E. coli, and S. typhi, 1 microg/ml for P. aeruginosa, and 5 microg/ml for S. marcescens. In contrast, exposure for 60 min was required to reach this percentage within phenylbutazone treated neutrophils. The minimum concentration to kill 90% of extracellular bacteria after 30 min was: 0.1 microg/ml for E. coli, P. aeruginosa and S. typhi, and 5 microg/ml, for S. marcescens. A positive interaction between ciprofloxacin and the O2-dependent mechanisms of phagocytes was found. The reactive oxygen metabolites produced in the respiratory burst did not affect the intraphagocytic activity of ciprofloxacin. Phenylbutazone treatment of phagocytes would be a good experimental model to study the intraphagocytic killing of drugs in situations such as AIDS and chronic granulomatous disease where inefficient oxidative mechanisms of neutrophils exist.
Levels of penicillin both in blood and CSF are determined in 11 children with meningococcal menin... more Levels of penicillin both in blood and CSF are determined in 11 children with meningococcal meningitis. Authors compare these values with MIC. The therapeutic pattern was 500.000 Ul/Kg/day of benzylpenicillin, in six doses, with a single initial doses of 200.000 Ul/Kg. The results recommend not to use a lower doses in order to assure a permanently efficient penicillin concentration.
Revista espanola de quimioterapia: publicacion oficial de la Sociedad Espanola de Quimioterapia
The post antibiotic effect (PAE) of 8 strains of Pseudomonas aeruginosa with different susceptibi... more The post antibiotic effect (PAE) of 8 strains of Pseudomonas aeruginosa with different susceptibility to sparfloxacin and ciprofloxacin was evaluated by the colony counting method using centrifugation to remove the antibiotic. The bacteria were exposed for 60 min to a quinolone concentration of 1 mg/ml. The MIC of sparfloxacin and ciprofloxacin ranged from 0.25-256 mg/ml and from 0. 25-128 mg/ml, respectively. PAE values ranged from 46 8.71 to 59.6 2.51 min and from 46.33 15.2 to 62.6 3.70 min, respectively. No significant statistical differences were found in the PAE duration for quinolones nor between strains. No correlation could be established between PAE and susceptibility of P. aeruginosa to quinolones.
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