ABSTRACT
Resumen Introducción. La política farmacéutica de Colombia establece la necesidad de intensificar la investigación en farmacoepidemiología a nivel nacional, especialmente en el caso de los antibióticos. Objetivo. Aportar información farmacoepidemiológica en cuanto a la efectividad, las condiciones de uso y la seguridad de la cefepima y el meropenem genéricos en un hospital de alta complejidad en Bogotá. Materiales y métodos. Se hizo un estudio descriptivo, longitudinal y retrospectivo sobre la utilización de estos medicamentos. Los datos se recolectaron de todas las historias clínicas en las cuales se registraba el uso de cefepima y meropenem. Resultados. Se incluyeron 82 pacientes tratados con cefepima y 91 con meropenem. La mayoría de ellos había estado internada en servicios diferentes a la unidad de cuidados intensivos (59,8 % con cefepima y 52,7 % con meropenem). El 21,9 % de los tratados con cefepima y el 49 % de los tratados con meropenem, tuvieron consulta con un infectólogo, en tanto que en 47 % de los primeros y en 78 % de los segundos, se hizo cultivo o antibiograma. Las condiciones más frecuentemente tratadas con cefepima fueron las infecciones de vías respiratorias (32,5 %) y, con meropenem, las infecciones genitourinarias (34,8 %). Las tasas de éxito terapéutico fueron de 61,7 % para la cefepima y de 63,0 % para el meropenem. Conclusiones. Este estudio aporta información sobre el desempeño terapéutico de dos antibióticos genéricos de uso hospitalario. No hubo reportes de falla terapéutica durante el periodo de estudio. En los casos en que no hubo respuesta al tratamiento, las causas frecuentes fueron las alteraciones farmacocinéticas, las condiciones clínicas desfavorables y la elección inadecuada del tratamiento antimicrobiano.
Abstract Introduction: The Colombian national pharmaceutical policy establishes as a strategy the generation of greater pharmaco-epidemiological research at the national level, especially in the case of antibiotic drugs. Objective: To provide local pharmaco-epidemiological evidence regarding the effectiveness, conditions of use and safety of generic meropenem and cefepime in a tertiary hospital in Bogotá. Materials and methods: We conducted a descriptive, longitudinal and retrospective drug utilization study. The data were collected from the medical histories of all the patients who had cefepime or meropenem prescribed. Results: We included 82 patients treated with cefepime and 91 treated with meropenem in the study. Most of the patients were in services different from the intensive care unit (taking cefepime: 59.8%, and meropenem: 52.7%). Only 21.9% of the patients treated with cefepime and 49% of those treated with meropenem were seen by an infectious disease specialist. The antibiogram was performed for 47% and 60% of the patients treated with cefepime and meropenem, respectively. The most frequent indication for cefepime were respiratory infections and for meropenem, genitourinary ones. Therapeutic success rates were 61.7% for cefepime and 63.0% for meropenem. Conclusions: This study contributes evidence regarding the therapeutic performance of two generic antibiotics used in tertiary hospitals. There were no reports of therapeutic failure during the study period. In the cases of non-response, pharmacokinetic alterations, unfavorable clinical conditions, and inappropriate choice of antimicrobial treatment were identified as frequent factors.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Young Adult , Drugs, Generic/therapeutic use , Tertiary Care Centers/statistics & numerical data , Cefepime/therapeutic use , Meropenem/therapeutic use , Anti-Bacterial Agents/therapeutic use , Drug Prescriptions/statistics & numerical data , Bacterial Infections/drug therapy , Retrospective Studies , Treatment Outcome , Drugs, Generic/adverse effects , Diagnosis-Related Groups , Colombia , Drug Utilization , Cefepime/adverse effects , Meropenem/adverse effects , Anti-Bacterial Agents/adverse effectsABSTRACT
Objective To investigate the resistance of Pseudomonas aeruginosa and genotyping of the main β-lactamases in China. Methods A total of 645 Pseudomonas aeruginosa isolates were collected from 28 hospitals in 16 cities in China from July 2006 to July 2007. The susceptibilities to 11 kinds of antimicrobial agents were detected by agar dilution or Kirby-Bauer disk diffusion method. The genotypes of β-lactamases including TEM, SHV, CTX-M and OXA of all the strains were detected by polymerase chain reaction (PCR) and sequence analysis. Results The resistance rates of 645 Pseudomonas aeruginosa isolates to antimicrobial agents were high, except those to amikacin and meropenem were lower than 30 %. Two hundred and seventy-five (42. 64 % ) strains were carbapenem and (or) meropenem-nonsusceptible Pseudomonas aeruginosa. Three hundred and sixty-eight (57.05 %) strains were multidrug-resistant Pseudomonas aeruginosa and 20 (3. 10%) strains were pandrug-resistant. The genotyping results of β-lactamases were as follows: 51 stains produced OXA-10 group β-lactamases, 37 were CARB type, 36 were TEM, 35 were PER, 11 were CTX-M, 9 were VEB, 5 were SHV, 24 were metallo-β-lactamases positive and 1 was GES. None of genotypes of plasmidmediated AmpC enzyme and other carbapenemases were detected. CTX-M-13, CTX-M-14,CTX-M-15, CTX-M-3 of extended spetrum β-lactamese were detected in Pseudomonas aeruginosa.Conclusions The situation of Pseudomonas aeruginosa resistances is severe in China. OXA-10 and PSE-1 are the most common genotypes of β-lactamases. The β-lactamases genotyping is different between carbapenem-nonsusceptible and carbapenem-susceptible strains.
ABSTRACT
Objective To study the genotypes of OXA-51-like carbepenemases in Aeinetobacter beumannii and its association with drug resistance. Methods The susceptibility of 174 Acinetobacter baumannii against ceftazidime, cefotriaxon, amikacin and ciprofloxacin were detected with disc diffusion method. The minimum inhibitory concentration (MIC) values for meropenem and imipenem were determined with an agar dilution method. VIM, IMP, OXA-23, OXA-24, OXA-51 and OXA-58 β-lactamase genes were determined by PCR. DNA sequencing and genotyping were performed against OXA-51 positivestrains. Results All 174 isolates were negative by PCR for genes OXA-24, OXA-58, IMP and VIM. OXA-23 and OXA-51were amplified in 15.5% (27/174) and 72.4% (126/174) isolates, respectively. Therewere 15.5% (27/174) isolates producing OXA-51-like and OXA-23 carbapenemase simultaneously. Among126 OXA-51-like carbapenemase producing strains, 82.5% (104/126)were OXA-66 genotype, whereas theremaining 17.5% (22/126) strains belong to other genotype. Eight novel OXA-51-like Genotype were foundin this study. Conclusions OXA-66 were the primary genotype of OXA-51-like carbapenemases in A.baumannii. OXA-66 were related to low-level carbapenems resistance and may be associated with resistanceof other drugs. We found new OXA-51-like genotype in clinic isolates of A. baumannii in this study.
ABSTRACT
Objective To study the effects of efflux pump inhibitors(CCCP and PAβN)on carbapenems in Pseudomonas aernginosa(P.aeruginosa)clinical isolates and investigate the association between the resistance to imipenem or meropenem and expression levels of efflux pumps of P.aeruginosa.Methods MICs of imipenem or meropenem combined with efflux pump inhibitors including carbonyl cyanide m-chlorophenylhydrazone(CCCP,107 strains)and Phe-Arg-β-naphthylamide(PAβN,71 strains)against imipenem-resistant strains were determined by agar dilution method,and changes of MICs were observed.For 32 strains with different resistant phenotypes to imipenem and meropenem,the mRNA expression levels of three efflux pump genes(mexA,mexD and mexF)were quantified by real time fluorescent quantitative PCR.Results The resistance rate of imipenem and meropenem didn't prove any significant difference in the presence of efflux pump inhibitors.The X2 value of imipenem combined with CCCP and PAβN were 0.338 and 0.086,respectively(P＞0.05),while that of meropenem combined with CCCP and PAβN were 1.065 and 1.458(P＞0.05).No significant in MICs of carbapenems were seen in over half of P. aeruginesa isolates. MICs of carbapenems was significantly downregulated for 4-fold or above in eight isolates. Overexpression of efflux pumps genes were present in 24 of 27 carbapenem-resistant isolates(88. 9% ). Efflux pumps genes including MexAB-OprM, MexCD-OprJ and MexEF-OprN were all overexpressed in 13 isolates,constituting 54. 2% of all carbapenem-resistant isolates. There were 3 isolates in which beth MexAB-OprM and MexCD-OprJ showed overexpression,constituting 12. 5%. Also,MexAB-OprM and MexEF-OprN overexpressed in 3 isolates. There were 2 isolates (8.3%) showing MexEF-OprN overexpression and MexAB-OprM alone. MexCD-OprJ didn't showed overexpression alone. Furthermore,the expression levels of efflux pumps genes mexA,mexD and mexF in isolates susceptible to both in imipenem and meropenem were 0. 48±0. 48,0. 48±0. 53 and 0. 30±0. 41,respectively,which were much lower than that in carbapenem-resistant ones (P＜0. 05 ). MexA gene was expressed at a higher level in meropenemresistant isolates than meropenem-susceptible ones (P＜0. 05 ). Conclusions When the concentration of CCCP and PAβN were 5 μg/ml and 20 μg/ml respectively,the efforts on the carhapenems resistance of P.aeruginosa were small Overexpression of MexAB-OprM might play an important role in meropenemresistance in P. aerugines. Overexpression of MexCD-OprJ and MexEF-OprN was associated with imipenemresistance. However,the relationship between them and meropenem-resistance need to be explored in the future.