Bismuth, esomeprazole, metronidazole, and minocycline or tetracycline as a first-line regimen for Helicobacter pylori eradication: A randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens.@*METHODS@#This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables.@*RESULTS@#As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups.@*CONCLUSION@#The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance.@*TRIAL REGISTRATION@#ClinicalTrials.gov, ChiCTR 1900023646.

Minocycline Activates the Nucleus of the Solitary Tract-Associated Network to Alleviate Lipopolysaccharide-Induced Neuroinflammation / 中国医学科学杂志(英文版)

Objective To examine the neuroanatomical substrates underlying the effects of minocycline in alleviating lipopolysaccharide (LPS)-induced neuroinflammation. Methods Forty C57BL/6 male mice were randomly and equally divided into eight groups. Over three conse-cutive days, saline was administered to four groups of mice and minocycline to the other four groups. Immediately after the administration of saline or minocycline on the third day, two groups of mice were additionally injected with saline and the other two groups were injected with LPS. Six or 24 hours after the last injection, mice were sacrificed and the brains were removed. Immunohistochemical staining across the whole brain was performed to detect microglia activation via Iba1 and neuronal activation via c-Fos. Morphology of microglia and the number of c-Fo-positive neurons were analyzed by Image-Pro Premier 3D. One-way ANOVA and Fisher's least-significant differences were employed for statistical analyses. Results Minocycline alleviated LPS-induced neuroinflammation as evidenced by reduced activation of microglia in multiple brain regions, including the shell part of the nucleus accumbens (Acbs), paraventricular nucleus (PVN) of the hypothalamus, central nucleus of the amygdala (CeA), locus coeruleus (LC), and nucleus tractus solitarius (NTS). Minocycline significantly increased the number of c-Fo-positive neurons in NTS and area postrema (AP) after LPS treatment. Furthermore, in NTS-associated brain areas, including LC, lateral parabrachial nucleus (LPB), periaqueductal gray (PAG), dorsal raphe nucleus (DR), amygdala, PVN, and bed nucleus of the stria terminali (BNST), minocycline also significantly increased the number of c-Fo-positive neurons after LPS administration. Conclusion Minocycline alleviates LPS-induced neuroinflammation in multiple brain regions, possibly due to increased activation of neurons in the NTS-associated network.

Hipomelanosis macular progresiva: respuesta al tratamiento con minociclina / Progressive macular hypomelanosis: response to treatment with minocycline

La hipomelanosis macular progresiva (HMP) es una dermatosis caracterizada por máculas hipopigmentadas, que se observa con mayor frecuencia en las mujeres y en los fototipos III y IV. Se ha asociado a Cutibacterium acnes (C. acnes) de tipo III como factor etiológico. Se presenta el caso de una paciente de 30 años, con máculas hipopigmentadas redondeadas en el tronco y la raíz de los miembros inferiores, de 10 años de evolución. El estudio histológico informó disminución del número de melanocitos y de pigmento melánico en la capa basal e infiltrado inflamatorio mononuclear perivascular superficial. Se indicó minociclina 100 mg/día por vía oral durante 8 meses, tras lo cual se observó la resolución total de las lesiones.

Progressive macular hypomelanosis (PMH) is a dermatosis characterized by hypopigmented macules, most frequently found in females and in phototypes III and IV. Cutibacterium acnes (C. acnes) type III has been associated as an etiological factor. We present the case of a thirty-year-old female patient with a 10-year history of nummular hypopigmented macules located on the top of the lower limbs and on the trunk. The histological study reported a decrease in the number of melanocytes and melanotic pigment in the basal layer and the presence of superficial perivascular mononuclear inflammatory infiltrate. After an 8-month regimen of oral minocycline 100 mg/day, there was a complete resolution of the lesions.

Anti-tumor activity of tigecycline: a review / 生物工程学报

Tigecycline is a novel glycylcycline antibacterial drug, which shows both antibiotic function and anti-tumor activity. This review summarizes the single and combined use of tigecycline for tumor treatment and the underpinning mechanisms. As an inhibitor for mitochondrial DNA translation, tigecycline affects the proliferation, migration, and invasion of tumor cells mainly through inhibiting mitochondrial protein synthesis and inducing mitochondrial dysfunction. Although the effect of tigecycline monotherapy is controversial, the efficacy of combined use of tigecycline is satisfactory. Therefore, it is important to explore the molecular mechanisms underpinning the anti-tumor activity of tigecycline, with the aim to use it as a cheap and effective new anti-tumor drug.

Regulatory mechanisms and therapeutic potential of microglial inhibitors in neuropathic pain and morphine tolerance / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Microglia are important cells involved in the regulation of neuropathic pain (NPP) and morphine tolerance. Information on their plasticity and polarity has been elucidated after determining their physiological structure, but there is still much to learn about the role of this type of cell in NPP and morphine tolerance. Microglia mediate multiple functions in health and disease by controlling damage in the central nervous system (CNS) and endogenous immune responses to disease. Microglial activation can result in altered opioid system activity, and NPP is characterized by resistance to morphine. Here we investigate the regulatory mechanisms of microglia and review the potential of microglial inhibitors for modulating NPP and morphine tolerance. Targeted inhibition of glial activation is a clinically promising approach to the treatment of NPP and the prevention of morphine tolerance. Finally, we suggest directions for future research on microglial inhibitors.

Minocycline inhibits formalin-induced inflammatory pain and the underlying mechanism / 北京大学学报(医学版)

OBJECTIVE@#To unravel the underlying mechanism of minocycline in formalin-induced inflammatory pain, and to investigate the effects of minocycline on synaptic transmission in substantia gela-tinosa (SG) neurons of rat spinal dorsal horn.@*METHODS@#Behavioral and immunohistochemistry experiments: 30 male Sprague-Dawley (SD) rats (3-5 weeks old) were randomly assigned to control (n=8 rats), model (n=8 rats), saline treatment model (n=6 rats) and minocycline treatment model (n=8 rats) groups. The control group was subcutaneously injected with normal saline on the right hindpaws. Acute inflammatory pain model was established by injecting 5% (volume fraction) formalin into the right hindpaws. The rats in the latter two groups received intraperitoneal injection of saline and minocycline 1 h before the formalin injection, respectively. The time of licking and lifting was recorded every 5 min within 1 h after the subcutaneous injection of normal saline or formalin for all the groups, which was continuously recorded for 1 h. One hour after the pain behavioral recording, the spinal cord tissue was removed following transcardial perfusion of 4% paraformaldehyde. The expression of c-Fos protein in spinal dorsal horn was observed by immunohistochemistry. Electrophysiological experiment: In vitro whole-cell patch-clamp recordings were performed in spinal cord parasagittal slices obtained from 26 male SD rats (3-5 weeks old). Two to five neurons were randomly selected from each rat for patch-clamp recording. the effects of minocycline, fluorocitrate and doxycycline on spontaneous excitatory postsynaptic currents (sEPSCs) or spontaneous inhibitory postsynaptic currents (sIPSCs) of SG neurons were investigated.@*RESULTS@#Compared with the control group, both the licking and lifting time and the expression of c-Fos protein in ipsilateral spinal dorsal horn of the model group were significantly increased. Intraperitoneal injection of minocycline largely attenuated the second phase of formalin-induced pain responses (t=2.957, P<0.05). Moreover, c-Fos protein expression was also dramatically reduced in both the superficial lamina (I-II) and deep lamina (III-IV) of spinal dorsal horn (tI-II=3.912, tIII-IV=2.630, P<0.05). On the other side, bath application of minocycline significantly increased the sIPSCs frequency to 220%±10% (P<0.05) of the control but did not affect the frequency (100%±1%, t=0.112, P=0.951) and amplitude (98%±1%, t=0.273, P=0.167) of sEPSCs and the amplitude (105%±3%, t=0.568, P=0.058) of sIPSCs. However, fluorocitrate and doxycycline had no effect on the frequency [(99%±1%, t=0.366, P=0.099); (102%±1%, t=0.184, P=0.146), respectively] and amplitude [(98%±1%, t=0.208, P=0.253); (99%±1%, t=0.129, P=0.552), respectively] of sIPSCs.@*CONCLUSION@#Minocycline can inhibit formalin-induced inflammatory pain and the expression of c-Fos protein in spinal dorsal horn. These effects are probably due to its enhancement in inhibitory synaptic transmission of SG neurons but not its effect on microglial activation or antibiotic action.

Antimicrobial susceptibility of Brazilian Clostridium difficile strains determined by agar dilution and disk diffusion

Abstract Clostridium difficile is a leading cause of diarrhea in hospitalized patients worldwide. While metronidazole and vancomycin are the most prescribed antibiotics for the treatment of this infection, teicoplanin, tigecycline and nitazoxanide are alternatives drugs. Knowledge on the antibiotic susceptibility profiles is a basic step to differentiate recurrence from treatment failure due to antimicrobial resistance. Because C. difficile antimicrobial susceptibility is largely unknown in Brazil, we aimed to determine the profile of C. difficile strains cultivated from stool samples of inpatients with diarrhea and a positive toxin A/B test using both agar dilution and disk diffusion methods. All 50 strains tested were sensitive to metronidazole according to CLSI and EUCAST breakpoints with an MIC90 value of 2 μg/mL. Nitazoxanide and tigecycline were highly active in vitro against these strains with an MIC90 value of 0.125 μg/mL for both antimicrobials. The MIC90 were 4 μg/mL and 2 μg/mL for vancomycin and teicoplanin, respectively. A resistance rate of 8% was observed for moxifloxacin. Disk diffusion can be used as an alternative to screen for moxifloxacin resistance, nitazoxanide, tigecycline and metronidazole susceptibility, but it cannot be used for testing glycopeptides. Our results suggest that C. difficile strains from São Paulo city, Brazil, are susceptible to metronidazole and have low MIC90 values for most of the current therapeutic options available in Brazil.

Worrisome trends in rising minimum inhibitory concentration values of antibiotics against methicillin resistant Staphylococcus aureus - Insights from a tertiary care center, South India

ABSTRACT INTRODUCTION: Appearance of isolated reports of resistance to anti-methicillin-resistantStaphylococcus aureus (MRSA) drugs is worrisome underscoring the need to continuously monitor the susceptibility of clinical MRSA isolates to these drugs. Hence, the present study is conducted to determine the susceptibility of MRSA isolates to various classes of anti-MRSA drugs such as vancomycin (glycopeptide), daptomycin (lipopeptide), tigecycline (glycylcycline), and linezolid (oxazolidinone) to determine the MIC50 and MIC90 values, and to observe MIC creep over a three year period, if any, with respect to these drugs. METHODS: A total of 200 isolates of MRSA obtained from clinical specimens were included. MIC was determined by E-test for anti-MRSA antibiotics vancomycin, linezolid, daptomycin, and tigecycline. Non-parametric methods (Kruskal-Wallis and Chi-square test) were used to assess MIC trends over time. In addition, MIC50 and MIC90 values were also calculated. RESULTS: No isolate was found resistant to vancomycin, daptomycin, or linezolid; five isolates were resistant to tigecycline. Seven VISA isolates were encountered with the MIC value for vancomycin of 4 µg/mL. MIC values for vancomycin, tigecycline, linezolid showed a definite increase over a 3-year period which was statistically significant with p-values <0.0001, 0.0032, 0.0242, respectively. When the percentage of isolates with a median MIC value less than or equal to that of the index year was calculated, the change was most striking with vancomycin. The proportion of isolates with higher MIC values was greater in 2014 than 2012 and 2013. CONCLUSION: MIC creep was notably observed with vancomycin, and to some extent with tigecycline and linezolid. Selection pressure may result in creeping MICs, which may herald the emergence of resistant organisms.

Resistencia a antibióticos de última línea en cocos Gram positivos: la era posterior a la vancomicina / Resistance to "last resort" antibiotics in Gram-positive cocci: The post-vancomycin era

En los últimos años se han desarrollado nuevas alternativas para el tratamiento de infecciones por patógenos Gram positivos multirresistentes, entre los cuales Staphylococcus aureus resistente a la meticilina (SARM) y los enterococos resistentes a la vancomicina (ERV) se consideran un verdadero reto terapéutico, y aunque el uso de la vancomicina en infecciones graves causadas por SARM ha generado serias dudas en los últimos años, continúa siendo escasa la información clínica de respaldo al uso de agentes terapéuticos que la superen en eficacia. El linezolid, la daptomicina y la tigeciclina son agentes que tienen actividad contra los cocos Gram positivos y que fueron aprobados e introducidos en la terapia clínica en la década pasada. Además, se han probado o están en las fases finales de desarrollo otros agentes como las cefalosporinas de última generación (ceftarolina y ceftobiprol). El propósito de esta revisión fue describir las nuevas alternativas terapéuticas, particularmente en la era posterior a la vancomicina, y repasar las características químicas más relevantes de los compuestos y su espectro de actividad, haciendo énfasis en sus mecanismos de acción y resistencia.

New therapeutic alternatives have been developed in the last years for the treatment of multidrug-resistant Gram-positive infections. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are considered a therapeutic challenge due to failures and lack of reliable antimicrobial options. Despite concerns related to the use of vancomycin in the treatment of severe MRSA infections in specific clinical scenarios, there is a paucity of solid clinical evidence that support the use of alternative agents (when compared to vancomycin). Linezolid, daptomycin and tigecycline are antibiotics approved in the last decade and newer cephalosporins (such as ceftaroline and ceftobiprole) and novel glycopeptides (dalvavancin, telavancin and oritavancin) have reached clinical approval or are in the late stages of clinical development. This review focuses on discussing these newer antibiotics used in the "post-vancomycin" era with emphasis on relevant chemical characteristics, spectrum of antimicrobial activity, mechanisms of action and resistance, as well as their clinical utility.

In vitro antimalarial activity of tigecycline against Plasmodium falciparum culture-adapted reference strains and clinical isolates from the Brazilian Amazon

Introduction: We evaluated the in vitro antimalarial activity of tigecycline as an alternative drug for the treatment of severe malaria. Methods: A chloroquine-sensitive Plasmodium falciparum reference strain, a chloroquine-resistant reference strain, and three clinical isolates were tested for in vitro susceptibility to tigecycline. A histidine-rich protein in vitro assay was used to evaluate antimalarial activity. Results: The geometric-mean 50% effective concentration (EC50%) of tigecycline was 535.5 nM (confidence interval (CI): 344.3-726.8). No significant correlation was found between the EC50% of tigecycline and that of any other tested antimalarial drug. Conclusions: Tigecycline may represent an alternative drug for the treatment of patients with severe malaria. .

pharmacodynamic simulation to evaluate tigecycline in treatment of nosocomial pneumonia caused by multidrug-resistant Acinetobacter baumannii

The shortage of effective antibiotics against multidrug-resistant Acinetobacter baumannii [MDR-Ab] has posed great threat to the public health. But the advent of tigecycline gives us new hope. The goal of our research was to assess the clinical efficacy of tigecycline at different doses by using a pharmacokinetic/pharmacodynamic [PK/PD] model which can incorporate pharmacokinetic data of tigecycline from patients with pneumonia and MICs of MDR-Ab from a tertiary hospital. A 10000-patient Monte-Carlo Simulation based on the PK/PD model was conducted to calculate the probability of target attainment [PTA] and the cumulative fraction of response [CFR] of tigecycline. 97% isolates displayed susceptibility and 3% were tigecycline-intermediate strains and the values of MIC ranged from 0.125 to 4microg/ml. A CFR of 61.62% was predicted for tigecycline at current dosage [50 mg q12h]. When the dosage was increased, the predicted CFRs for 75 mg q12h, 100 mg q12h, 125 mg q12h, 150 mg q12h were 81.00%, 89.86%, and 94.57%, 96.77%, respectively. Despite presented higher susceptibility, the CFR obtained was not optimal at current dosage. A higher CFR indicating a better clinical efficacy can be gained by the increased dosage.

In vitro antibacterial activity of tigecycIine against clinical isolates of linezolid-Intermediate and linezolid-resistant enterococci by time-kill assay

Introduction: Enterococci have become the third leading cause of nosocomial bacteraemia, an infection which is significantly associated with the risk of developing infective endocarditis. Linezolid provides high rates of clinical cure and microbiologic success in complicated infections due to Enterococcus spp. However, several instances of emergence of resistance during linezolid treatment have been reported. The aim of this study was evaluate the activity of tigecycline against linezolidintermediate (LIE) and linezolid-resistant enterococcus faecalis(LRE) by the timekill assay. Methods: Five isolates of LRE and two isolates of LIE were used in this study. Minimum inhibitory concentration (MIC) was determined by broth dilution following the guidelines from the Clinical and Laboratory Standards Institute (CLSI). Time-kill assay was employed to access the in vitro response profile of tigecycline. Results: All seven isolates presented MIC of 0.125 ìg/mL. Tigecycline activity was individually evaluated according to CLSI criteria. This antibiotic showed bactericidal activity against three of the five isolates of LRE and bacteriostatic activity against the other isolates. Conclusions: Tigecycline presented both bacteriostatic and bactericidal activity against tested isolates, which is an important data that must be considered for new studies.

Minocycline, but not ascorbic acid, increases motor activity and extends the life span of Drosophila melanogaster / La minociclina, pero no el ácido ascórbico, incrementa la actividad motora y extiende el período de vida de Drosophila melanogaster

In the present study we compared the effects of minocycline and ascorbic acid in the life span, motor activity and lipid peroxidation of Drosophila melanogaster, in an effort to find a substance capable of providing protection against oxidative stress in aging. In the flies treated with minocycline a very significant increase in the life span (101 ± 1.33 days) was observed when compared to those treated with ascorbic acid and controls (42.3% and 38.4%, respectively). The motor activity of minocycline treated flies also increased significantly with respect to control and ascorbic acid fed flies, from the 3rd to the 9th week of treatment. With regard to lipid peroxidation, it was found that the levels of malondialdehyde (MDA) in flies treated with minocycline showed no statistical differences to the control on the first day of treatment, but a significantly lower content on the day of 50% survival. In contrast, in flies treated with ascorbic acid significantly elevated levels of MDA compared to control and minocycline treated flies were detected throughout. These results suggest a protective effect of minocycline against oxidative stress and aging in D. melanogaster. An inhibitory effect on reactive oxygen species production may be an important contributing factor.

En el presente estudio se compararon los efectos del ácido ascórbico y la minociclina en la duración del periodo de vida, la actividad motora y la peroxidación lipídica de Drosophila melanogaster en un esfuerzo por encontrar una sustancia capaz de proporcionar protección contra el estrés oxidativo en el envejecimiento. En las moscas tratadas con minociclina se observó un aumento significativo en la duración de la vida (101 ± 1,33 días) en comparación con los tratados con ácido ascórbico y los controles (42,3% y 38,4%, respectivamente). La actividad motora de las moscas tratadas con minociclina aumentó significativamente cuando se comparó con las tratadas con ácido ascórbico y el control, desde la 3ra hasta la 9na semana de tratamiento. Con respecto a la peroxidación lipídica, se encontró que los niveles de malondialdehído (MDA) en moscas tratadas con minociclina no mostraron diferencias estadísticas con relación al control en el primer día de tratamiento; sin embargo, se detecto una disminución significativa de la concentración de MDA cuando se alcanzó el 50% de sobrevida. En contraste, en moscas tratadas con ácido ascórbico observamos que los niveles de MDA estaban significativamente elevados, cuando se compararon con las moscas tratadas con minociclina y el control a lo largo de todo el tratamiento. Estos resultados sugieren un efecto protector de la minociclina frente al estrés oxidativo y el envejecimiento en D. melanogaster, aunque un efecto inhibidor sobre la producción de especies reactivas del oxígeno puede ser un factor contribuyente importante.

Antimicrobial Susceptibility of Stenotrophomonas maltophilia Isolates from Korea, and the Activity of Antimicrobial Combinations against the Isolates

The aim of this study was to determine antimicrobial susceptibility of recent clinical Stenotrophomonas maltophilia isolates from Korea, and to compare the activity levels of several combinations of antimicrobials. A total of 206 non-duplicate clinical isolates of S. maltophilia was collected in 2010 from 11 university hospitals. Antimicrobial susceptibility testing was performed using the Clinical Laboratory Standards Institute agar dilution method. In vitro activity of antimicrobial combinations was tested using the checkerboard method. The susceptibility rates to trimethoprim-sulfamethoxazole and minocycline were 96% and 99%, respectively. The susceptibility rate to levofloxacin was 64%. All of four antimicrobial combinations showed synergy against many S. maltophilia isolates. A combination of trimethoprim-sulfamethoxazole plus ticarcillin-clavulanate was most synergistic among the combinations. None of the combinations showed antagonistic activity. Therefore, some of the combinations may be more useful than individual drugs in the treatment of S. maltophilia infection. Further clinical studies are warranted to validate our in vitro test results.

Antimicrobial Susceptibility of Stenotrophomonas maltophilia Isolates from a Korean Tertiary Care Hospital

We determined the antimicrobial susceptibility of 90 clinical isolates of Stenotrophomonas maltophilia collected in 2009 at a tertiary care hospital in Korea. Trimethoprim-sulfamethoxazole, minocycline, and levofloxacin were active against most of the isolates tested. Moxifloxacin and tigecycline were also active and hold promise as therapeutic options for S. maltophilia infections.

Estudio multicéntrico de la vigilancia de la susceptibilidad in vitro a tigeciclina en Santiago de Chile / Multicenter study on the monitoring of in vitro susceptibility to tigeeyeline in Santiago, Chile

The objective of this multicenter study was to determine tigeeyeline susceptibility rates, measured by agar diffusion, in nine hospitals in Santiago and to compare these rates with other antimicrobials. Each center studied 20 strains per month. All intermedíate and fully resistant strains as well as 10 percent of susceptibile strains were also studied by the broth microdilution method. Overall, 2301 strains were studied displaying the foliowing susceptibility rates for tigeeyeline: 100 percent for Streptococcus sp, Enterococcus sp, and E. coli respectively, 99.8 percent for Staphylococcus sp, 93 percent for Klebsiella and 80 percent for Acinetobacter baumarmii. For Proteus, Providencia and Morganella the susceptibility rates were 4 percent. For cefotaxime-resistant Klebsiella and imipenem-resistant A. baumarmii susceptibility rates were 95 percent and 80 percent respectively. The agar diffusion and broth dilution method were 100 percent concordant for tigeeyeline susceptible strains but only 27 percent for resistant or intermedíate strains represented mostly by Acinetobacter baumannii. The majority of these strains (57/59) proved to be susceptible after retesting. The great majority (96,6 percent) of strains tested from nine Chilean hospitals proved to be susceptible to tigeeyeline with exception for Proteus, Providencia and Morganella (66 percent resistance). Using the agar diffusion method for measuring tigeeyeline susceptibility to A. baumannii may be misleading.

Para conocer la susceptibilidad a tigeciclina por difusión en agar en nueve hospitales de Santiago y comparar la susceptibilidad con otros antimicrobianos, se diseñó este estudio multicéntrico. Cada centro estudió 20 cepas mensualmente. Las intermedias, resistentes y 10 por cientoo de las susceptibles se re-testearon y estudiaron por microdilución en caldo. Se incluyeron 2.304 cepas. Fueron susceptibles a tigeciclina Strep-tococcus sp (100 por cientoo), Enterococcus sp (100 por ciento), E. coli (100 por cientoo), Staphylococcus sp (99,8 por ciento), Klebsiella pneumoniae (93 por ciento) y Acinetobacter baumannii (80 por ciento). En Proteus, Providencia y Morganella la susceptibilidad fue 4 por cientoo. Klebsiella resistente a cefotaxima y Acinetobacter resistente a imipenem, 95 por cientoo y 80 por cientoo fueron susceptibles a tigeciclina, respectivamente. La concordancia en cepas susceptibles y en las enviadas como resistentes o intermedias (A. baumannii) fue 100 por cientoo y 27 por cientoo respectivamente. El re-testeo confirmó que la mayoría eran susceptibles. Los patrones de susceptibilidad bacteriana muestran muy buena actividad in vitro a tigeciclina. La resistencia in vitro de A. baumannii por difusión en agar debe interpretarse con precaución.

Tetracycline and oxytetracycline resistance determinants detected in Bacillus cereus strains isolated from honey samples / Detección de determinantes de resistencia a tetraciclina y oxitetraciclina en cepas de Bacillus cereus aisladas de muestras de miel

The aim of this study was to investigate the presence of tetracycline and oxytetracycline resistance determinants in Bacillus cereus strains isolated from honey samples. Of a total of 77 isolates analyzed, 30 (39%) exhibited resistance to tetracyclines according to the results of a disk diffusion method. Resistant strains (n=30) were screened by PCR for the presence of the resistant determinants tetK, tetL, tetM, tetO, tetW, otrA and otrB and their MIC values for tetracycline, oxytetracycline and minocycline were assessed. According to the PCR results, 23 isolates (77%) presented at least one tetracycline or oxytetracycline resistance determinant. The tetK genotype was present in 10 isolates while the tetL, tetM, and otrA genotypes were present in 3, 2, and 5 isolates, respectively. In addition, 2 isolates of the tetK plus tetM genotype, 1 of the tetK plus tetL genotype, and 1 of the tetK plus otrA genotype were found. All isolates were tetW, tetO and otrB negatives. On the other hand, 7 isolates (23%) showed a tetracycline-resistant and/or minocyclineresistant phenotype (MIC) but did not carry any of the tet or otr determinants investigated in this study. This research has shown that B. cereus isolates from honey samples contain a variety of tetracycline and oxytetracycline resistance genes, including the tetK and tetL determinants which encode for efflux proteins, and tetM and otrA, which encode for ribosomal protection proteins. These findings indicate that strains isolated from honeys could represent a reservoir for tetracycline resistance genes. To our knowledge, this is the first report of tetracycline-resistant and oxytetracyclineresistant B. cereus strains carrying the tetK determinant, and also the first report of oxytetracycline-resistant and tetracycline- resistant Bacillus species carrying the otrA determinant.

El objetivo del presente estudio ha sido investigar la presencia de diversos determinantes de resistencia a tetraciclina y oxitetraciclina en las poblaciones de Bacillus cereus presentes en la miel. De un total de 77 aislamientos evaluados, 30 (39%) resultaron resistentes a tetraciclina y/o minociclina de acuerdo con los resultados de las pruebas de difusión en disco. Dentro del grupo que presentó un fenotipo resistente, se investigó la presencia de los determinantes tetK, tetL, tetM, tetO, tetW, otrA y otrB por PCR y se determinaron los valores de CIM para tetraciclina, oxitetraciclina y minociclina. De acuerdo con los resultados obtenidos por PCR, 23 aislamientos (77%) presentaron al menos un determinante de resistencia a tetraciclina o a oxitetraciclina; el genotipo tetK se encontró en 10 de esos aislamientos, mientras que los genotipos tetL, tetM y otrA se hallaron en 3, 2 y 5 aislamientos, respectivamente. Ningún aislamiento presentó los genotipos tetW, tetO ni otrB. Adicionalmente, se encontraron los genotipos tetK plus tetM (2 aislamientos); tetK plus tetL (1 aislamiento) y tetK plus otrA (1 aislamiento). Por otra parte, 7 cepas (23%) resultaron resistentes a tetraciclina, oxitetraciclina y/o minociclina por CIM, pero no presentaban ninguno de los determinantes tet u otr estudiados. Estos resultados indican la existencia de un alto porcentaje de cepas de B. cereus aisladas de miel con genes de resistencia a tetraciclina y oxitetraciclina, incluyendo los determinantes tetK, tetL, tetM y otrA. Este estudio constituye el primer registro de la presencia del determinante tetK de resistencia a tetraciclina en B. cereus, como así también la presencia del determinante otrA dentro del género Bacillus.