Andres Zuluaga | Universidad de Antioquia (original) (raw)
Papers by Andres Zuluaga
PLOS ONE, 2015
Some generics of antibacterials fail therapeutic equivalence despite being pharmaceutical equival... more Some generics of antibacterials fail therapeutic equivalence despite being pharmaceutical equivalents of their innovators, but data are scarce with antifungals. We used the neutropenic mice model of disseminated candidiasis to challenge the therapeutic equivalence of three generic products of fluconazole compared with the innovator in terms of concentration of the active pharmaceutical ingredient, analytical chemistry (liquid chromatography/mass spectrometry), in vitro susceptibility testing, single-dose serum pharmacokinetics in infected mice, and in vivo pharmacodynamics. Neutropenic, five week-old, murine pathogen free male mice of the strain Udea:ICR(CD-2) were injected in the tail vein with Candida albicans GRP-0144 (MIC = 0.25 mg/L) or Candida albicans CIB-19177 (MIC = 4 mg/L). Subcutaneous therapy with fluconazole (generics or innovator) and sterile saline (untreated controls) started 2 h after infection and ended 24 h later, with doses ranging from no effect to maximal effect (1 to 128 mg/kg per day) divided every 3 or 6 hours. The Hill's model was fitted to the data by nonlinear regression, and results from each group compared by curve fitting analysis. All products were identical in terms of concentration, chromatographic and spectrographic profiles, MICs, mouse pharmacokinetics, and in vivo pharmacodynamic parameters. In conclusion, the generic products studied were pharmaceutically and therapeutically equivalent to the innovator of fluconazole.
BMC Research Notes, 2015
Previously, we validated the mouse thigh infection model to test the therapeutic equivalence of g... more Previously, we validated the mouse thigh infection model to test the therapeutic equivalence of generic antibiotic products. Here, our aim was to compare the in vivo efficacy of amikacin products in clinical use in Colombia using this animal model. All except one generic product had the same in vitro potency, judging by the lack of differences on MIC and MBC compared with the innovator. However, eight of nine generic products failed in the neutropenic mouse thigh infection model to achieve the innovator's maximum effect (E max ≤ 5.65 for the generics vs. 6.58 log10 CFU/g for the innovator) against Escherichia coli SIG-1, after subcutaneous treatment every 6 h with doses ranging from 1.5 to 3072 mg/kg per day. As we demonstrated previously with other antibiotics such as vancomycin, gentamicin and oxacillin, the generic products of amikacin failed the in vivo efficacy testing. The therapeutic equivalence should be assessed in vivo before clinical approval of generic products.
Background: 19 GP of GNT are licensed for human use in Colombia. Research with amikacin demonstra... more Background: 19 GP of GNT are licensed for human use in Colombia. Research with amikacin demonstrated that most GP do not have therapeutic equivalence (TE) with the OC, even if criteria for pharmaceutical equivalence (PE) were fulfilled. Here, we report data for GP of GNT. Methods: PE for all GP was determined by microbiologic assay with Antibiotic Medium # 11 as seeding agar and S. epidermidis ATCC 12228 as testing organism, comparing their standard curves against the OC and pure GNT (Sigma) by linear curve fitting analysis (CFA). Broth microdilution MIC / MBC against E. coli SIG-1 and P. aeruginosa ATCC 27853 were compared by Kruskal-Wallis. For the NMTIM, we used 6 week-old, 25±2 g MPF Udea:ICR(CD-1) female mice infected with E. coli SIG-1. Primary pharmacodynamic parameters (PDP) Emax, ED50, and slope were calculated by least squares nonlinear regression (NLR) with the sigmoid dose-response model and used to compute secondary PDP bacteriostatic dose (BD) and the doses needed to k...
Background: Contrary to accepted dogma, recent animal model data with GP demonstrated that pharma... more Background: Contrary to accepted dogma, recent animal model data with GP demonstrated that pharmaceutical equivalence (PE) does not predict TE for penicillin G, ampicillin, oxacillin, amikacin, and lincomycin. Here, we report PE and TE of 5 GP of TAX legally marketed in Colombia. Methods: PE was determined by microbiologic assays using Antibiotic Medium 1 as seeding agar and S. aureus ATCC 6538p as testing organism, comparing their standard curves against the OC by curve fitting analysis (CFA). MIC / MBC by broth microdilution against E. coli SIG-1 and P. aeruginosa ATCC 27853 were compared by Kruskal-Wallis test. For the NMTIM, we used 6 week-old, 25±2 g MPF female mice of the strain Udea:ICR(CD-1) infected with E. coli SIG-1. Primary pharmacodynamic parameters (PDP) Emax, ED50, and Hill’s slope were calculated by least squares nonlinear regression (NLR) applied to the sigmoid dose-response model and used to compute secondary PDP bacteriostatic dose (BD) and the doses needed to kil...
Iatreia
El modelo murino de infección del muslo emplea animales neutropénicos para poder determinar la ef... more El modelo murino de infección del muslo emplea animales neutropénicos para poder determinar la eficacia intrínseca de los antibióticos in vivo. Sin embargo, no se ha definido el número de neutrófilos y la duración de la neutropenia inducida por ciclofosfamida (CFM) intraperitoneal (IP), información fundamentalpara valorar la reproducibilidad y confiabilidad del modelo.
Iatreia
La equivalencia farmacéutica (EF) como prueba de equivalencia terapéutica (ET) para productos gen... more La equivalencia farmacéutica (EF) como prueba de equivalencia terapéutica (ET) para productos genéricos parenterales (PG) es un dogma ampliamente difundido y aceptado, pero nunca se ha retado experimentalmente [1]. Comparamos la magnitud de los parámetros farmacodinámicos (PD) de los genéricos de lincomicina (LIN) con los del compuesto original (CO), mediante determinación de su eficacia bactericida in vitro e in vivo.
Background: Legal use of GP in human and veterinary medicine has great impact in price regulation... more Background: Legal use of GP in human and veterinary medicine has great impact in price regulation worldwide, but numbers of GP makers are increasing overwhelmingly. Beyond quality problems, concern is growing about the scientific basis of using bioequivalence (BE) as surrogate proof of TE, the accepted dogma. To test it, bactericidal efficacy of GP of PEN made in Colombia was compared in vitro and in vivo against the original compound (OC) in simultaneous experiments, employing the same methods required for new antimicrobials. Methods: Microbiologic assays with S. aureus ATCC 6538p and broth microdilution minimal inhibitory and bactericidal concentrations (MIC/MBC) were used to determine BE by comparison of standard curves (SC) and in vitro activity. The NMTIM used 6 week-old specific pathogen free ICR:CD-1 female mice weighting 25±2 g infected with S. aureus GRP-0057, a PEN-susceptible clinical isolante. The sigmoid dose-response model was applied to calculate by least squares nonl...
Background: WHO accepts the use of GP without demonstration of therapeutic equivalence (TE) provi... more Background: WHO accepts the use of GP without demonstration of therapeutic equivalence (TE) providing the same CAP and similar serum pharmacokinetics. For medicines with narrow therapeutic range stricter crieteria apply, but iv antibiotics are not so considered. However, there are 3 instead of 2 participants in infectious diseases: host, drug and microorganism, with wide variation between them. We used the NMTIM to determine TE of all GP of OXA legally commercialized in Colombia. Methods: Microbiologic assays with S. aureus ATCC 6538p determined CAP by comparison of standard curves (SC). In vitro activity was measured by broth microdilution minimal inhibitory and bactericidal concentrations (MIC/MBC). The NMTIM used ICR:CD-1 female mice (25±2 g) infected with S. aureus GRP-0057, a wild type clinical isolate. Pharmacodynamic parameters (PDP) like Emax, bacteriostatic dose (BD) and the dose needed to kill 1 log (1LKD) were calculated by least squares nonlinear regression (NLR). SC wer...
Background: The NMTIM has been fundamental in turning out the knowledge of antimicrobial pharmaco... more Background: The NMTIM has been fundamental in turning out the knowledge of antimicrobial pharmacology. LIN is still widely used in developing countries, where GP have replaced the original compound (OC) with official support and encouragement from regulatory and health agencies around the world, but clinical use of GP is not preceded by experimental demostration of therapeutical equivalence (TE). We used the NMTIM to determinate TE of all GP of LIN legally commercialized in Colombia. Methods: Microbiologic assays with M. luteus ATCC 9341 measured concentration of the active principle in GP by comparison of their standard curves (SC) with that of the OC. In vitro activity was determined by broth microdilution minimal inhibitory and bactericidal concentration (MIC/MBC). For each product, the NMTIM used at least 10 treated and 6 untreated ICR:CD-1 female mice (25±2g ) infected with S. aureus GRP-0057, a wild type clinical isolate. Pharmacodynamics parameters (PDP) like Emax and the dos...
Background: we have shown that generic products (GP) of VAN have lesser in vivo efficacy than the... more Background: we have shown that generic products (GP) of VAN have lesser in vivo efficacy than the original compound (OC) against S. aureus despite identical in vitro activity. We aimed to determine if GP favor the emergence of VAN resistant subpopulations compared with OC. Methods: Susceptibility of a clinical MRSA strain to VAN 1, 2, 3, 4 & 5 mg/L was characterized by population analysis profile before and after 12 cycles of VAN treatment (1200 mg/kg/24h SQ q3h) in the NMTIM. For each cycle, groups of 2 mice, inoculated with ~107 CFU/thigh, were treated with OC, 3 GP or sterile saline (SS). After 24 h, bacteria were recovered and re-inoculated to new animals. The proportion of resistant cells (PRC) at each concentration and the area under the bacterial growth versus VAN concentration curve (AUC) were calculated for each group. Pre-post PRC differences were compared by t-test, and AUC changes by ANOVA of the intensity of the effect (IE) using SS group as untreated control (IE = AUCC...
Background: WHO accepts the use of GP without demonstration of TE if good manufacturing practices... more Background: WHO accepts the use of GP without demonstration of TE if good manufacturing practices, identical concentration of active phar maceutical ingredient (cAPI) and similar PK (waived for iv generics) are fulfilled. However, this assumption has not been challenged experimentally. We compared in vitro and in vivo efficacy of 3 GP of AS against the OC. Methods: Potency and cAPI were determined by microbiologic assays (MA) with Antibiotic Medium No. 8 and M. luteus ATCC 9341 and E. coli GRP-0108 as testing organisms for ampicillin and sulbactam components respectively, comparing their standard curves against the OC by linear curve fitting analysis (CFA). In vitro activity was compared by broth microdilution MIC/MBC against E. coli SIG-1 by Kruskal-Wallis test (KW). The NMTIM used ICR female mice (23-27 g) infected with E. coli SIG-1. To compare efficacy of each GP against the OC, we employed CFA of their nonlinear regressions derived from the Hill model. In case of violation of p...
Background: Drug regulatory agencies worldwide have supported the replacement of OC by GP to redu... more Background: Drug regulatory agencies worldwide have supported the replacement of OC by GP to reduce healthcare expenses. However, their approval requirements for intravenous antibiotics are lim-ited to pharmaceutical in vitro tests, shunning any in vivo study. Previously, we showed that for lincomycin, pharmaceutical equivalence does not guarantee therapeutic equivalence. Considering the wide use of clindamycin and the pivotal role of the NMTIM for understanding antimicrobial pharmacology, we aimed to use this model to compare in vivo efficacy of all CLI GP legally marketed in Colombia with the OC. Methods: The NMTIM used ICR:CD-1 female mice, 25±2 g, infected with S. aureus GRP-0057, a wild-type clinical isolate. Primary pharmacodynamic parameters (PDP) Emax, ED50, and slope were calculated by least squares nonlinear regression with Hill's dose-response model and used to compute secondary PDP bacteriostatic dose (BD) and the doses needed to kill 1 (1LKD) and 2 logs (2LKD). Indi...
Background: Snake-bite is a common public health problem in tropical and subtropical countries, c... more Background: Snake-bite is a common public health problem in tropical and subtropical countries, causing important physical and psychological sequelae. In Colombia, Bothrops spp are responsible for 90-95% of accidents and 7-15% of them develop an infectious complication. Many authors support the early administration of empirical antibiotics; however, others consider that their benefit is questionable. Our aim was to compare the frequency of infections associated with ophidism between two non-concurrent cohorts. Methods: From 2003 to 2007, 254 patients were attended for snake-bite in our University Hospital. 160 patients fulfilling inclusion criteria were divided in 2 groups: (a) exposed (who received >1 dose of the same antibiotic in the first 48h after snake-bite) (b) non-exposed. We determined epidemiological, clinical, laboratory and therapeutic features at the primary attention site, at the University Hospital and two weeks after snake-bite. Dichotomic variables were analyzed ...
Background: WHO and most regulatory agencies accept generic drugs' bioequivalence (BE) as sur... more Background: WHO and most regulatory agencies accept generic drugs' bioequivalence (BE) as surrogate proof of TE with the original product. To challenge that assumption, efficacy of all GP of AMP legally distributed in Colombia was compared in vitro and in vivo against the OC in simultaneous experiments. Methods: Microbiologic assays with M. luteus ATCC 9341 and broth microdilution minimal inhibitory and bactericidal concentrations (MIC/MBC) were used to determine BE by comparison of standard curves (SC) and in vitro antimicrobial activity. The NMTIM employed 6 week-old specific pathogen free ICR:CD-1 female mice weighting 25±2 g infected with E. coli SIG-1, a wild type strain. The sigmoid dose-response model was applied to calculate by least squares nonlinear regression (NLR) pharmacodynamic parameters (PDP) like Emax and the dose needed to kill 1 log (1LKD). SC were compared by linear curve fitting analysis (CFA), whole NLR by nonlinear CFA, individual PDP by nonlinear CFA and ...
PLOS ONE, 2015
Some generics of antibacterials fail therapeutic equivalence despite being pharmaceutical equival... more Some generics of antibacterials fail therapeutic equivalence despite being pharmaceutical equivalents of their innovators, but data are scarce with antifungals. We used the neutropenic mice model of disseminated candidiasis to challenge the therapeutic equivalence of three generic products of fluconazole compared with the innovator in terms of concentration of the active pharmaceutical ingredient, analytical chemistry (liquid chromatography/mass spectrometry), in vitro susceptibility testing, single-dose serum pharmacokinetics in infected mice, and in vivo pharmacodynamics. Neutropenic, five week-old, murine pathogen free male mice of the strain Udea:ICR(CD-2) were injected in the tail vein with Candida albicans GRP-0144 (MIC = 0.25 mg/L) or Candida albicans CIB-19177 (MIC = 4 mg/L). Subcutaneous therapy with fluconazole (generics or innovator) and sterile saline (untreated controls) started 2 h after infection and ended 24 h later, with doses ranging from no effect to maximal effect (1 to 128 mg/kg per day) divided every 3 or 6 hours. The Hill's model was fitted to the data by nonlinear regression, and results from each group compared by curve fitting analysis. All products were identical in terms of concentration, chromatographic and spectrographic profiles, MICs, mouse pharmacokinetics, and in vivo pharmacodynamic parameters. In conclusion, the generic products studied were pharmaceutically and therapeutically equivalent to the innovator of fluconazole.
BMC Research Notes, 2015
Previously, we validated the mouse thigh infection model to test the therapeutic equivalence of g... more Previously, we validated the mouse thigh infection model to test the therapeutic equivalence of generic antibiotic products. Here, our aim was to compare the in vivo efficacy of amikacin products in clinical use in Colombia using this animal model. All except one generic product had the same in vitro potency, judging by the lack of differences on MIC and MBC compared with the innovator. However, eight of nine generic products failed in the neutropenic mouse thigh infection model to achieve the innovator's maximum effect (E max ≤ 5.65 for the generics vs. 6.58 log10 CFU/g for the innovator) against Escherichia coli SIG-1, after subcutaneous treatment every 6 h with doses ranging from 1.5 to 3072 mg/kg per day. As we demonstrated previously with other antibiotics such as vancomycin, gentamicin and oxacillin, the generic products of amikacin failed the in vivo efficacy testing. The therapeutic equivalence should be assessed in vivo before clinical approval of generic products.
Background: 19 GP of GNT are licensed for human use in Colombia. Research with amikacin demonstra... more Background: 19 GP of GNT are licensed for human use in Colombia. Research with amikacin demonstrated that most GP do not have therapeutic equivalence (TE) with the OC, even if criteria for pharmaceutical equivalence (PE) were fulfilled. Here, we report data for GP of GNT. Methods: PE for all GP was determined by microbiologic assay with Antibiotic Medium # 11 as seeding agar and S. epidermidis ATCC 12228 as testing organism, comparing their standard curves against the OC and pure GNT (Sigma) by linear curve fitting analysis (CFA). Broth microdilution MIC / MBC against E. coli SIG-1 and P. aeruginosa ATCC 27853 were compared by Kruskal-Wallis. For the NMTIM, we used 6 week-old, 25±2 g MPF Udea:ICR(CD-1) female mice infected with E. coli SIG-1. Primary pharmacodynamic parameters (PDP) Emax, ED50, and slope were calculated by least squares nonlinear regression (NLR) with the sigmoid dose-response model and used to compute secondary PDP bacteriostatic dose (BD) and the doses needed to k...
Background: Contrary to accepted dogma, recent animal model data with GP demonstrated that pharma... more Background: Contrary to accepted dogma, recent animal model data with GP demonstrated that pharmaceutical equivalence (PE) does not predict TE for penicillin G, ampicillin, oxacillin, amikacin, and lincomycin. Here, we report PE and TE of 5 GP of TAX legally marketed in Colombia. Methods: PE was determined by microbiologic assays using Antibiotic Medium 1 as seeding agar and S. aureus ATCC 6538p as testing organism, comparing their standard curves against the OC by curve fitting analysis (CFA). MIC / MBC by broth microdilution against E. coli SIG-1 and P. aeruginosa ATCC 27853 were compared by Kruskal-Wallis test. For the NMTIM, we used 6 week-old, 25±2 g MPF female mice of the strain Udea:ICR(CD-1) infected with E. coli SIG-1. Primary pharmacodynamic parameters (PDP) Emax, ED50, and Hill’s slope were calculated by least squares nonlinear regression (NLR) applied to the sigmoid dose-response model and used to compute secondary PDP bacteriostatic dose (BD) and the doses needed to kil...
Iatreia
El modelo murino de infección del muslo emplea animales neutropénicos para poder determinar la ef... more El modelo murino de infección del muslo emplea animales neutropénicos para poder determinar la eficacia intrínseca de los antibióticos in vivo. Sin embargo, no se ha definido el número de neutrófilos y la duración de la neutropenia inducida por ciclofosfamida (CFM) intraperitoneal (IP), información fundamentalpara valorar la reproducibilidad y confiabilidad del modelo.
Iatreia
La equivalencia farmacéutica (EF) como prueba de equivalencia terapéutica (ET) para productos gen... more La equivalencia farmacéutica (EF) como prueba de equivalencia terapéutica (ET) para productos genéricos parenterales (PG) es un dogma ampliamente difundido y aceptado, pero nunca se ha retado experimentalmente [1]. Comparamos la magnitud de los parámetros farmacodinámicos (PD) de los genéricos de lincomicina (LIN) con los del compuesto original (CO), mediante determinación de su eficacia bactericida in vitro e in vivo.
Background: Legal use of GP in human and veterinary medicine has great impact in price regulation... more Background: Legal use of GP in human and veterinary medicine has great impact in price regulation worldwide, but numbers of GP makers are increasing overwhelmingly. Beyond quality problems, concern is growing about the scientific basis of using bioequivalence (BE) as surrogate proof of TE, the accepted dogma. To test it, bactericidal efficacy of GP of PEN made in Colombia was compared in vitro and in vivo against the original compound (OC) in simultaneous experiments, employing the same methods required for new antimicrobials. Methods: Microbiologic assays with S. aureus ATCC 6538p and broth microdilution minimal inhibitory and bactericidal concentrations (MIC/MBC) were used to determine BE by comparison of standard curves (SC) and in vitro activity. The NMTIM used 6 week-old specific pathogen free ICR:CD-1 female mice weighting 25±2 g infected with S. aureus GRP-0057, a PEN-susceptible clinical isolante. The sigmoid dose-response model was applied to calculate by least squares nonl...
Background: WHO accepts the use of GP without demonstration of therapeutic equivalence (TE) provi... more Background: WHO accepts the use of GP without demonstration of therapeutic equivalence (TE) providing the same CAP and similar serum pharmacokinetics. For medicines with narrow therapeutic range stricter crieteria apply, but iv antibiotics are not so considered. However, there are 3 instead of 2 participants in infectious diseases: host, drug and microorganism, with wide variation between them. We used the NMTIM to determine TE of all GP of OXA legally commercialized in Colombia. Methods: Microbiologic assays with S. aureus ATCC 6538p determined CAP by comparison of standard curves (SC). In vitro activity was measured by broth microdilution minimal inhibitory and bactericidal concentrations (MIC/MBC). The NMTIM used ICR:CD-1 female mice (25±2 g) infected with S. aureus GRP-0057, a wild type clinical isolate. Pharmacodynamic parameters (PDP) like Emax, bacteriostatic dose (BD) and the dose needed to kill 1 log (1LKD) were calculated by least squares nonlinear regression (NLR). SC wer...
Background: The NMTIM has been fundamental in turning out the knowledge of antimicrobial pharmaco... more Background: The NMTIM has been fundamental in turning out the knowledge of antimicrobial pharmacology. LIN is still widely used in developing countries, where GP have replaced the original compound (OC) with official support and encouragement from regulatory and health agencies around the world, but clinical use of GP is not preceded by experimental demostration of therapeutical equivalence (TE). We used the NMTIM to determinate TE of all GP of LIN legally commercialized in Colombia. Methods: Microbiologic assays with M. luteus ATCC 9341 measured concentration of the active principle in GP by comparison of their standard curves (SC) with that of the OC. In vitro activity was determined by broth microdilution minimal inhibitory and bactericidal concentration (MIC/MBC). For each product, the NMTIM used at least 10 treated and 6 untreated ICR:CD-1 female mice (25±2g ) infected with S. aureus GRP-0057, a wild type clinical isolate. Pharmacodynamics parameters (PDP) like Emax and the dos...
Background: we have shown that generic products (GP) of VAN have lesser in vivo efficacy than the... more Background: we have shown that generic products (GP) of VAN have lesser in vivo efficacy than the original compound (OC) against S. aureus despite identical in vitro activity. We aimed to determine if GP favor the emergence of VAN resistant subpopulations compared with OC. Methods: Susceptibility of a clinical MRSA strain to VAN 1, 2, 3, 4 & 5 mg/L was characterized by population analysis profile before and after 12 cycles of VAN treatment (1200 mg/kg/24h SQ q3h) in the NMTIM. For each cycle, groups of 2 mice, inoculated with ~107 CFU/thigh, were treated with OC, 3 GP or sterile saline (SS). After 24 h, bacteria were recovered and re-inoculated to new animals. The proportion of resistant cells (PRC) at each concentration and the area under the bacterial growth versus VAN concentration curve (AUC) were calculated for each group. Pre-post PRC differences were compared by t-test, and AUC changes by ANOVA of the intensity of the effect (IE) using SS group as untreated control (IE = AUCC...
Background: WHO accepts the use of GP without demonstration of TE if good manufacturing practices... more Background: WHO accepts the use of GP without demonstration of TE if good manufacturing practices, identical concentration of active phar maceutical ingredient (cAPI) and similar PK (waived for iv generics) are fulfilled. However, this assumption has not been challenged experimentally. We compared in vitro and in vivo efficacy of 3 GP of AS against the OC. Methods: Potency and cAPI were determined by microbiologic assays (MA) with Antibiotic Medium No. 8 and M. luteus ATCC 9341 and E. coli GRP-0108 as testing organisms for ampicillin and sulbactam components respectively, comparing their standard curves against the OC by linear curve fitting analysis (CFA). In vitro activity was compared by broth microdilution MIC/MBC against E. coli SIG-1 by Kruskal-Wallis test (KW). The NMTIM used ICR female mice (23-27 g) infected with E. coli SIG-1. To compare efficacy of each GP against the OC, we employed CFA of their nonlinear regressions derived from the Hill model. In case of violation of p...
Background: Drug regulatory agencies worldwide have supported the replacement of OC by GP to redu... more Background: Drug regulatory agencies worldwide have supported the replacement of OC by GP to reduce healthcare expenses. However, their approval requirements for intravenous antibiotics are lim-ited to pharmaceutical in vitro tests, shunning any in vivo study. Previously, we showed that for lincomycin, pharmaceutical equivalence does not guarantee therapeutic equivalence. Considering the wide use of clindamycin and the pivotal role of the NMTIM for understanding antimicrobial pharmacology, we aimed to use this model to compare in vivo efficacy of all CLI GP legally marketed in Colombia with the OC. Methods: The NMTIM used ICR:CD-1 female mice, 25±2 g, infected with S. aureus GRP-0057, a wild-type clinical isolate. Primary pharmacodynamic parameters (PDP) Emax, ED50, and slope were calculated by least squares nonlinear regression with Hill's dose-response model and used to compute secondary PDP bacteriostatic dose (BD) and the doses needed to kill 1 (1LKD) and 2 logs (2LKD). Indi...
Background: Snake-bite is a common public health problem in tropical and subtropical countries, c... more Background: Snake-bite is a common public health problem in tropical and subtropical countries, causing important physical and psychological sequelae. In Colombia, Bothrops spp are responsible for 90-95% of accidents and 7-15% of them develop an infectious complication. Many authors support the early administration of empirical antibiotics; however, others consider that their benefit is questionable. Our aim was to compare the frequency of infections associated with ophidism between two non-concurrent cohorts. Methods: From 2003 to 2007, 254 patients were attended for snake-bite in our University Hospital. 160 patients fulfilling inclusion criteria were divided in 2 groups: (a) exposed (who received >1 dose of the same antibiotic in the first 48h after snake-bite) (b) non-exposed. We determined epidemiological, clinical, laboratory and therapeutic features at the primary attention site, at the University Hospital and two weeks after snake-bite. Dichotomic variables were analyzed ...
Background: WHO and most regulatory agencies accept generic drugs' bioequivalence (BE) as sur... more Background: WHO and most regulatory agencies accept generic drugs' bioequivalence (BE) as surrogate proof of TE with the original product. To challenge that assumption, efficacy of all GP of AMP legally distributed in Colombia was compared in vitro and in vivo against the OC in simultaneous experiments. Methods: Microbiologic assays with M. luteus ATCC 9341 and broth microdilution minimal inhibitory and bactericidal concentrations (MIC/MBC) were used to determine BE by comparison of standard curves (SC) and in vitro antimicrobial activity. The NMTIM employed 6 week-old specific pathogen free ICR:CD-1 female mice weighting 25±2 g infected with E. coli SIG-1, a wild type strain. The sigmoid dose-response model was applied to calculate by least squares nonlinear regression (NLR) pharmacodynamic parameters (PDP) like Emax and the dose needed to kill 1 log (1LKD). SC were compared by linear curve fitting analysis (CFA), whole NLR by nonlinear CFA, individual PDP by nonlinear CFA and ...