RESUMEN
Carbapenem-resistant Enterobacterales (CRE) have become a major public health problem worldwide. The aim of this study was to investigate efficacy of ceftazidime/avibactam and plazomicin on carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates. Susceptibility of imipenem, meropenem, ertapenem, ceftazidime/avibactam and plazomicin was investigated by broth-microdilution method. Major carbapenemases NDM, VIM, IMP, KPC, OXA-48 as well as other ß-lactamases namely, TEM, SHV, OXA-1-like, CTX-M, ACC, FOX, MOX, DHA, CIT, EBC, VEB, GES, PER were investigated by PCR. A total of 120 carbapenem-resistant isolates (60 E. coli and 60 K. pneumoniae) were included in this study and blaOXA-48-like was found in 78.33%, blaNDM in 26.66%, blaKPC in 7.5%, blaIMP in 5.83%, and blaVIM in 5%. Among 94 isolates with the blaOXA-48-like gene, 22.3% were resistant to ceftazidime/avibactam and 51.1% were resistant to plazomicin. Of 32 isolates with blaNDM, 31 (96.9%) were resistant to ceftazidime/avibactam and 30 (93.75%) were resistant to plazomicin, and both antibiotics had limited effects against blaNDM carriers (P < 0.001). Of the 12 isolates with blaNDM+OXA-48 combination, 11 (91.7%) were resistant to ceftazidime/avibactam and plazomicin. The effect of both antibiotics was significantly lower in strains with blaNDM+OXA-48 combination (P < 0.005).The most common carbapenemase genes in this study were blaOXA-48-like and blaNDM. Ceftazidime/avibactam demonstrated a good efficacy among OXA-48 producing K. pneumoniae and E. coli, however, plazomicin had a significantly lower antibacterial effect in our study. Both antimicrobial agents should be considered as an option by evaluating combined susceptibility results and gene patterns obtained by regional and global molecular data in the treatment of CRE infections.
Asunto(s)
Antibacterianos , Compuestos de Azabiciclo , Enterobacteriaceae Resistentes a los Carbapenémicos , Ceftazidima , Combinación de Medicamentos , Escherichia coli , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Sisomicina , beta-Lactamasas , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Ceftazidima/farmacología , Compuestos de Azabiciclo/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Antibacterianos/farmacología , Sisomicina/farmacología , Sisomicina/análogos & derivados , beta-Lactamasas/genética , Humanos , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Proteínas Bacterianas/genética , Carbapenémicos/farmacología , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/tratamiento farmacológicoRESUMEN
Opportunistic fungal infections like invasive candidiasis and aspergillozis have high mortality rate particularly in immunosupressive patients. The rate of therapy success with antifungal agents is usually low. Although immunotherapy methods have been developed to increase the host response against antifungals, there has been a need for new antifungal therapeutic agents in the treatment of invasive aspergillozis and other opportunistic fungal infections. Mycoviruses are the viruses that specifically infect fungi. The use of mycoviruses in the treatment of invasive fungal infections has not been suggested yet. However, as mentioned in this review, the researches about the use of mycoviruses as a therapeutic agent have been still carried on. Mycoviruses have no infectivity as free particules. Many of them have RNA genome. They are classified as: Fungi containing "double stranded (ds) RNA, ds DNA or single stranded RNA". Although most of them are found in plant pathogenic fungi, they are also found in human pathogenic fungi. In most of the mycoviruses identified up to now, dsRNA genome are present. Mycoviruses that can be pathogenic for human and carrying dsRNA genome have been classified as Partitiviridae, Totiviridae, Chrysoviridae, Reoviridae and Hypoviridae. A part of mycoviruses may not cause any sign of infection in fungal host. The other part of mycoviruses causes hypovirulence or lethal effect. When hypovirulence occured in fungi, the observed effects are the decrease in pigmentation, mycelium formation, asexual sporulation, growing rate and the loss of fertility. The transfer of mycovirus to fungi may occur by intracellular or extracellular way. The transfer of genetic content to fungi occurs in two way: transformation and transfection. In both ways, there is a need for a spheroblast that has no cell wall. There are various scenarios about mycoviruses for the their use in the treatment. In the first scenario, the transfer of selective mycovirus is ensured by extracellular way, and then the binding of mycovirus to target fungus by genetic modifications is aimed. The second scenario is about the use of mycovirus as a vector for genetic transformation. In fact, this method is applied by using toxins in fungal diseases of plants. In addition, the production of lethal antibodies or peptides derived from antibodies obtained from toxin-coding cytoplasmic dsRNA mycovirus toxins may be a new therapeutic approach. It has been claimed that these derivatives may be used as parentheral therapeutic agents against human pathogenic fungi including Candida albicans. In this review article, the importance of mycoviruses in mycology has been discussed.
Asunto(s)
Virus Fúngicos/fisiología , Hongos/virología , Huésped Inmunocomprometido , Micosis/terapia , Infecciones Oportunistas/terapia , Virus Fúngicos/clasificación , Virus Fúngicos/genética , Humanos , Micosis/microbiología , Infecciones Oportunistas/microbiologíaRESUMEN
Candida species are generally identified by conventional methods such as germ tube or morphological appearance on corn meal agar, biochemical methods using API kits and molecular biological methods. Alternative to these methods, rapid and accurate identification methods of microorganisms called matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has recently been described. In this study, Candida identification results by API Candida kit, API 20C AUX kit and identifications on corn meal agar (CMA) are compared with the results obtained on Vitek-MS. All results were confirmed by sequencing internal transcribed spacer (ITS) regions of rDNA. Totally, 97 Candida strains were identified by germ tube test, CMA, API and Vitek-MS. Vitek-MS results were compatible with 74.2 % of API 20C AUX and 81.4 % of CMA results. The difference between the results of API Candida and API 20C AUX was detected. The ratio of discrepancy between Vitek-MS and API 20C AUX was 25.8 %. Candida species mostly identified as C. famata or C. tropicalis by and not compatible with API kits were identified as C. albicans by Vitek-MS. Sixteen Candida species having discrepant results with Vitek-MS, API or CMA were randomly chosen, and ITS sequence analysis was performed. The results of sequencing were compatible 56.2 % with API 20C AUX, 50 % with CMA and 93.7 % with Vitek-MS. When compared with conventional identification methods, MS results are more reliable and rapid for Candida identification. MS system may be used as routine identification method in clinical microbiology laboratories.
Asunto(s)
Candida/clasificación , Candida/aislamiento & purificación , Técnicas Microbiológicas/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , ADN de Hongos/química , ADN de Hongos/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Análisis de Secuencia de ADN , Factores de TiempoRESUMEN
Immunosuppressive patients are at risk of fungal and bacterial infections. Therefore, these patients receive prophylactic, preemptive, empirical or target antifungal and concomitant antibiotic therapy. To this end, caspofungin (CAS) or voriconazole (VRC) antifungals and cefoperazone-sulbactam (CPZ/SAM) or piperacillin-tazobactam (PIP/TAZ) antibiotics may be used. Here, we aimed to investigate the interaction between these antifungals and antibiotics by in vitro and in vivo methods. The interaction was tested by chequerboard analysis and fractional inhibitory concentration index (FICI). It was also tested in a neutropenic mice-invasive candidiasis model and evaluated by fungal burden in kidney tissue of infected animals from the first day to the fifth day of treatment with 24 h intervals. A synergism was detected between CAS and CPZ/SAM (FICI = 0.1) and PIP/TAZ (FICI = 0.3). Fungal burden in tissues of drug-treated mice was reduced compared with controls in a time-dependent manner. In comparison with CAS-alone treated group, there were 1.32 log10 reductions of fungal burden in CAS + CPZ/SAM (p = 0.002) and in CAS + PIP/TAZ group (p = 0.14). The same interactions were not found with VRC and antibiotics. CPZ/SAM had stronger synergistic interaction with CAS than PIP/TAZ. The mechanism of synergism is not well understood. This is most likely due to an increase in the anticandidal effect of CAS plus antibiotics.
Asunto(s)
Cefoperazona/farmacología , Equinocandinas/farmacología , Ácido Penicilánico/análogos & derivados , Pirimidinas/farmacología , Sulbactam/farmacología , Triazoles/farmacología , Animales , Antibacterianos/farmacología , Antifúngicos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Candida albicans/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Caspofungina , Interacciones Farmacológicas , Femenino , Lipopéptidos , Ratones , Ratones Endogámicos BALB C , Ácido Penicilánico/farmacología , Piperacilina/farmacología , Combinación Piperacilina y Tazobactam , VoriconazolRESUMEN
The aim of this study was to determine the esterase activity of clinically important Candida species and to evaluate tween 80 opacity test medium as an additional identification method. A total of 118 Candida isolates (86 C. albicans, 12 C. tropicalis, 5 C. glabrata, 4 C. krusei, 3 C. guilliermondii, 3 C. kefyr, 3 C. parapsilosis, 1 C. famata, 1 C. dubliniensis) were examined for their response to tween 80 opacity test. Our results showed that, 83 of 86 (96.5%) Candida albicans, and all of the C. tropicalis and C. guilliermondii strains (100%) yielded a halo around their colonies. The remaining Candida species did not produce a positive test response after 13 days of incubation. It can be concluded that, tween 80 opacity test is a simple and economical test that can be used as a supplementary test for the identification of Candida species.