Actividad in vitro del tedizolid y de antibióticos de comparación en aislamientos de Staphylococcus aureus resistentes a meticilina en infecciones de piel y tejidos blandos en siete hospitales de Colombia / In vitro activity of tedizolid and other comparator drugs in methicillin-resistant Staphylococcus aureus isolates in skin and soft tissue infections in seven Colombian hospitals

Introducción. Staphylococcus aureus resistente a meticilina (SARM) causa infecciones graves de la piel y los tejidos blandos en los hospitales y, en los últimos años, en la comunidad. El tedizolid es una nueva oxazolidinona cuya potencia in vitro ha demostrado ser mayor que la del linezolid frente a este microorganismo. Objetivo. Conocer la actividad antimicrobiana del tedizolid y de algunos antibióticos de comparación en aislamientos de SARM causante de infecciones de piel y tejidos blandos en hospitales de Colombia. Materiales y métodos. Se hizo un estudio multicéntrico prospectivo y descriptivo a lo largo de doce meses en siete hospitales de tercer nivel de Colombia. Se recolectaron aislamientos de SARM de pacientes adultos con infección de piel y tejidos blandos. Se determinó la concentración inhibitoria mínima (CIM) mediante la técnica de ETEST® (bioMérieux) del tedizolid, el linezolid, la vancomicina, la daptomicina, el trimetoprim-sulfametoxazol y la clindamicina. Resultados. Se obtuvieron aislamientos de SARM de 102 pacientes, de los cuales 56 (54,9 %) eran hombres; el promedio de edad fue de 46,8 años. La infección tuvo origen en la comunidad en 77 casos (75,4 %). El tipo de muestra que predominó fue el absceso (69 pacientes: 67,6 %). Todos los aislamientos fueron sensibles a tedizolid, linezolid, daptomicina, trimetoprim-sulfametoxazol y vancomicina. La actividad in vitro del tedizolid fue mayor que la del linezolid. Los intervalos de la CIM del tedizolid oscilaron entre 0,125 µg/ml y 0,5 µg/ml en tanto que los del linezolid fluctuaron entre 1 µg/m y 2 µg/ml. Conclusiones. Las cepas circulantes de SARM en Colombia presentaron una gran sensibilidad al tedizolid, por lo cual sería una alternativa terapéutica para las infecciones de piel y tejidos blandos en nuestro medio.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) causes severe skin and soft tissue infections in hospitals and, more recently, in the community. Tedizolid is a new second-generation oxazolidinone derivative having greater in vitro potency than linezolid against this type of microorganism. Objectives: To evaluate the antimicrobial activity of tedizolid and other comparator antibiotics in MRSA isolates causing skin and soft tissue infections in Colombian hospitals. Materials and methods: We conducted a prospective, multi-center descriptive study in seven tertiary-level hospitals in Colombia along a 12-month period. MRSA isolates were collected from adult patients with skin and soft tissue infections. Tedizolid, linezolid, vancomycin, daptomycin, trimethoprimsulfamethoxazole, and clindamycin minimum inhibitory concentration (MIC) was determined by ETEST® (bioMérieux). Results: MRSA isolates were obtained from 102 patients with an average age of 46.8 years of whom 56 (54.9%) were men. Infection was community-acquired in 77 cases (75.4%). Abscess-related samples predominated (69 patients: 67.6%). All isolates were susceptible to tedizolid, linezolid, daptomycin, trimethoprim-sulfamethoxazole, and vancomycin. Tedizolid had greater in vitro activity than linezolid. Tedizolid MIC intervals ranged from 0.125 µg/mL to 0.5 µg/mL while those of linezolid ranged from 1µg/mL to 2µg/mL. Conclusions: MRSA strains circulating in Colombia are highly susceptible to tedizolid and can be considered a therapeutic alternative for hospitals and/or community-acquired skin and soft tissue infections.

Onychomatricoma: a tumor unknown to dermatologists

A sixty-one year old white female was referred to the Dermatology Department to treat an ingrown nail in the inner corner of the left hallux. Examination of the entire nail unit showed the presence of xanthonychia in the outer corner besides thickening and increase in the transverse curvature of the nail plate. Dermoscopy and nuclear magnetic resonance of the free edge of the nail plate detected characteristic signs of onychomatricoma, a diagnosis that was later confirmed by anatomopathological exam.

In vitro susceptibility to methicillin, vancomycin and linezolid of staphylococci isolated from bloodstream infections in eastern Turkey

Staphylococcus species are one of the major causes of bacterial bloodstream infections. Multi-resistant staphylococci infections are major therapeutic problems. This study was aimed to detect methicillin, linezolid and vancomycin susceptibilities of Staphylococcus isolates. A total of 870 Staphylococcus strains isolated from blood cultures of hospitalized patients with BSI. Antimicrobial susceptibilities of methicillin, linezolid and vancomycin were detected according to the Clinical and Laboratory Standards Institute (CLSI). A total of 771 (88.6%) isolates were coagulase-negative staphylococci (CoNS). 700 (80.5%) isolates were methicillin-resistant (MR) and 170 (19.5%) were methicillin-susceptible (MS). All the MS isolates were also susceptible to linezolid. However 15 (1.7%) of MR strains were resistant to linezolid. The minimum inhibitory concentration range for the linezolid-resistant isolates by Etest was 6-32 µg/mL. The difference between linezolid susceptibilities for MS and MR staphylococci was not quite statistically significant (p = 0.052). There was no statistically significant difference between S. aureus and CoNS isolates for linezolid susceptibility. All of the isolates were susceptible to vancomycin. In conclusion, linezolid is currently an efficient option for the treatment of methicillin-resistant staphylococci infections.

Colistin and anti-Gram-positive bacterial agents against Acinetobacter baumannii

Introduction Acinetobacter baumannii has attained an alarming level of resistance to antibacterial drugs. Clinicians are now considering the use of older agents or unorthodox combinations of licensed drugs against multidrug-resistant strains to bridge the current treatment gap. We investigated the in vitro activities of combination treatments that included colistin with vancomycin, norvancomycin or linezolid against multidrug-resistant Acinetobacter baumannii. Methods The fractional inhibitory concentration index and time-kill assays were used to explore the combined effects of colistin with vancomycin, norvancomycin or linezolid against 40 clinical isolates of multidrug-resistant Acinetobacter baumannii. Transmission electron microscopy was performed to evaluate the interactions in response to the combination of colistin and vancomycin. Results The minimum inhibitory concentrations (MICs) of vancomycin and norvancomycin for half of the isolates decreased below the susceptibility break point, and the MIC of linezolid for one isolate was decreased to the blood and epithelial lining fluid concentration using the current dosing regimen. When vancomycin or norvancomycin was combined with subinhibitory doses of colistin, the multidrug-resistant Acinetobacter baumannii test samples were eradicated. Transmission electron microscopy revealed that subinhibitory doses of colistin were able to disrupt the outer membrane, facilitating a disruption of the cell wall and leading to cell lysis. Conclusions Subinhibitory doses of colistin significantly enhanced the antibacterial activity of vancomycin, norvancomycin, and linezolid against multidrug-resistant Acinetobacter baumannii. .

Sensibilidad antimicrobiana in vitro en aislamientos de Enterococcus faecalis y Enterococcus faecium obtenidos de pacientes hospitalizados / In vitro antimicrobial susceptibility in Enterococcus faecalis and Enterococcus faecium isolated from hospitalized patients

Introducción. Actualmente se considera a Enterococcus spp. como uno de los agentes de infección hospitalaria más importantes, siendo su resistencia a los antibióticos un problema importante en los centros de salud. Objetivos. Caracterizar la resistencia antimicrobiana en 50 cepas de Enterococcus spp. aisladas de muestras clínicas de pacientes hospitalizados . Materiales y métodos. Se llevó a cabo un estudio de tipo descriptivo observacional de corte transversal en 50 aislamientos clínicos de estas especies microbianas. Se trabajó un aislamiento por paciente. La identificación y la sensibilidad a los antibióticos se realizaron por métodos automatizados y convencionales. El análisis fenotípico de los mecanismos de resistencia a glucopéptidos se hizo según las recomendaciones de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Resultados. De 50 aislamientos, 30 (60,0 %) y 20 (40,0 %) pertenecían a las especies de Enterococcus faecalis y Enterococcus faecium, respectivamente. La resistencia global expresada por este género fue de 38/50 (76,0 %) para ampicilina; 33/50 (66,0 %) para gentamicina de alto nivel; 34/50 (68,0 %) para estreptomicina de alto nivel; 26/50 (52,0 %) para ciprofloxacina; 4/50 (8,0 %) para linezolid; 17/50 (34,0 %) para teicoplanina; 25/50 (50,0 %) para vancomicina; 31/50 (62,0 %) para minociclina; 34/50 (68,0 %) para tetraciclina y 9/50 (18,0 %) para nitrofurantoina. Frente a los glucopéptidos, 25/50 (50,0 %) y 10/50 (20,0 %) de los aislamientos presentaron los mecanismos Van A y Van B, respectivamente. Conclusiones. Podemos concluir que la mayoría de las veces, las cepas aisladas en el Hospital Hermanos Ameijeiras mostraron porcentajes de resistencia por encima de lo reportado en la literatura científica consultada. El alto porcentaje de cepas con resistencia a la vancomicina podría influir en la aparición de otros gérmenes Gram positivos con resistencia a este fármaco. Se reporta por primera vez en un hospital cubano resistencia de E. faecium a linezolid.

Introduction: Enterococcus spp is currently considered as one of the most important nosocomial pathogens . The antibiotic resistance of this group of bacteria is a particularly important problem in health centers. Objective: To characterize the antibiotic resistance of 50 Enterococcus spp strains isolated from hospitalized patients clinical samples. Materials and methods: We conducted a cross-sectional descriptive observational study in 50 clinical isolates of Enterococcus spp. Only one isolate per patient was analyzed . The identification and antibiotic susceptibility were studied by conventional and automated methods . The phenotypic analysis of glycopeptide resistance mechanisms was performed as recommended by the Spanish Society of Clinical Microbiology and Infectious Diseases . Results: Of 50 isolates obtained from clinical samples, 30 ( 60.0%) belonged to Enterococcus faecalis and 20 (40.0 %) to Enterococcus faecium . The global resistance expressed by this genre was as follows: Ampicillin, 38/50 ( 76.0%); high-level gentamicin, 33/50 ( 66.0%); high-level streptomycin, 34/50 (68.0 %) ; ciprofloxacin, 26/50 (52.0 %); linezolid, 4/50 (8.0 %); teicoplanin, 17/50 ( 34.0%); vancomycin, 25/50 (50.0 %); minocycline, 31/50 ( 62.0%); tetracycline, 34/50 (68.0 %); nitrofurantoin, 9/50 ( 18.0%). As regards glycopeptides, 25/50 (50.0%) showed a Van A mechanism and 10/50 (20.0 %) a Van B mechanism . Conclusions: The isolates obtained at Hospital Hermanos Ameijeiras showed higher resistance rates than those reported in the consulted literature. The high percentage of vancomycin-resistant strains might have influenced the development of other Gram-positive bacteria resistant to this drug. This is the first report on Enterococcus faecium resistant to linezolid in a Cuban hospital.

Screening bioactive compounds inhibiting influenza virus from isatidis radix by ultrafiltration mass spectrometry / 中国中药杂志

In vitro neuraminidase inhibition assays and ultrafiltration liquid chromatography with diodearray detector coupled to time of flight mass spectrometer (UPLC-DAD-TOF-MS) were combined to screen bioactive compounds inhibiting neuraminidase from Isatidis Radix. By comparing the compounds from Isatidis Radix before and after ultrafiltration, we found that arginine, goitrin and adenosinea can bind with neuraminidase, and the binding degree of the three compounds were (36.23 +/- 1.12)%, (32.54 +/- 1.02)% and (9.38 +/- 0.47)%, respectively. The IC50 of arginine and goitrin were (1.16 +/- 0.02), (1.20 +/- 0.02) g x L(-1), respectively. While the IC50 of adenosinea was higher than 500 g x L(-1). The results showed that arginine and goitrin might be the main compounds with antiviral activity of Isatidis Radix. This study may provide a useful method for the screening of bioactive compounds and quality control of Isatidis Radix.

Neumonía secundaria a Staphylococcus aureus resistente a la meticilina / Pneumonía associated with Staphylococcus aureus methicillin resistant

Pneumonia associated with Staphylococcus aureus resistant to methicillin has emerged as an important pathogen in children without established risk factors and prevalence worldwide is increasing. This organism is capable of causing severe invasive disease with there commitment to optimal and timely treatment should be established promptly. The decision to start treatment is based on empirical knowledge of the local prevalence of susceptibility pattern, the severity of the infection and the risk factors and the host. Therapeutic alternatives primarily in children include vancomycin, clindamycin, linezolid, and trimethoprim/sulfamethoxazole.

La neumonía asociada a Staphylococcus aureus resistente a la meticilina ha emergido como un patógeno importante en niños sin establecerse factores de riesgo y su prevalencia a nivel mundial va en ascenso. Este organismo es capaz de causar enfermedad invasiva con compromiso severo de allí que el tratamiento óptimo y oportuno debe de establecerse con prontitud. La decisión de iniciar tratamiento empírico se basa en el conocimiento de la prevalencia local del patrón de susceptibilidad, la severidad de la infección y los factores e riesgo del huésped. Las alternativas terapéuticas en niños incluyen fundamentalmente vancomicina, clindamicina, linezolid y trimetropin/sulfametoxazol.

Novel actions of oxazolidinones: in vitro screening of a triazolyloxazolidinone for anticonvulsant activity

To test the hypothesis that a triazolyloxazolidinone [PH084] has anticonvulsant activity by examining its effects on in vitro seizure models in the rat hippocampus. Whole-cell synaptic currents, action potentials and extracellular population spikes [PS] were recorded in the cell body area of rat hippocampal CA1 region in acutely prepared slices. Chemical [picrotoxin [100 micro m] and zero magnesium] and electrical seizures were induced and the effect of PH084 [10 micro M] was tested on cellular responses, multiple spikes and spontaneous bursting frequencies. PH084 depressed evoked excitatory postsynaptic currents, action potential firing frequency and PS amplitude. All of these responses did not recover to baseline after 15-20 min washout of PH084. Perfusion with zero magnesium ion [Mg[2+]]-containing buffer converted a single PS to multiple PS [mPS] accompanied by spontaneous burst. PH084 suppressed the mPS and the spontaneous burst frequency and it also suppressed the picrotoxin-induced mPS number. However, it did not affect the frequency of stimulus train-induced after discharge or bursts. Furthermore, 8-10 min pretreatment with PH084 did not affect the ability of zero Mg[2+] buffer, picrotoxin or stimulus train to induce epileptiform activity. Thus, while PH084 may have potential for anticonvulsant activity against chemically induced seizures, it has little or no potential against electrically induced seizures or in preventing epileptiform discharge

Multidrug- resistant tuberculosis treatment with linezolid-containing regimen

The following is a case of multidrug-resistant pulmonary tuberculosis [MDR-TB] that was treated successfully with a linezolid-containing regimen. It was found that linezolid is an efficient medicine for MDR-TB treatment with an acceptable side effect profile. Treatment was maintained for 18 months, and closely monitoring toxicities did not reveal evidence of any neurologic adverse effects. However, despite our expectation, thrombocytopenia was seen after 2 years follow-up

Retrospective analysis of the Gram-positive bacteria-infected cases in the Department of Hematology / 中国实验血液学杂志

This study was purposed to evaluate the efficacy and safety of linezolid, vancomycin and teicoplanin for the treatment of patients infected by Gram-positive bacteria in the Department of Hematology by retrospective analysis. The patients with fever in our department from January to December in 2011 were selected for blood culture with Gram-positive bacteria and treated with linezolid, vancomycin or teicoplanin alone.Various parameters were recorded before and after treatment, such as fever time, respiratory symptoms, physical signs, radiographic changes, blood and biochemical routine, and adverse reactions. The efficacy and safety of linezolid, vancomycin and teicoplanin were compared according to the fever abating time, bacterial clearance rate, clinical efficiencies and adverse events. The patients were divided into linezolid group (15 patients), vancomycin group (17 patients) and teicoplanin group (20 patients). The results showed that the mean time of fever abating in linezolid group was (4.43 ± 3.15)d, bacterial clearance rate and clinical efficiency in linezolid group were 55.56% and 86.67%, respectively. The above three data in vancomycin group were (6.83 ± 4.67)d, 54.54% and 76.47% respectively, and were (5.57 ± 4.16)d, 41.67% and 80.00% in teicoplanin group respectively. There was no statistically significant difference between three groups (P > 0.05). There were one case of diarrhea and two cases of thrombocytopenia in the linezolid group, and one case of nausea and two cases of creatinine increase in the vancomycin group. There were three cases of thrombocytopenia in the teicoplanin group. The thrombocytopenia in five cases and the hemogram drop in patients with leukemia after treatment were overlapped, their drug treatment did not stop, but their thrombocytopoiesis recovered to normal-level, thus the drug treatment were considered as no relation with thrombocytopenia. It is concluded that the treatment efficacy between linezolid, vancomycin and teicoplanin for Gram-positive bacterial infections is not statistically different, but linezolid maybe have advantage over vancomycin and teicoplanin in fever abating time, bacterial clearance rate and clinical efficiency.

Clinical Characteristics of Community Acquired Enterococcal Urinary Tract Infections In Children

PURPOSE: Recently, enterococcus spp. have become one of the most common nosocomial pathogens with increasing rates of multi-drug resistance. However, study on enterococcal urinary tract infections (UTIs) in children is very limited, especially community acquired UTIs. We studied the clinical characteristics of enterococcus spp. in community acquired UTIs and antibiotic resistance within our urban area. METHODS: All children with first episode of community acquired UTIs due to enterococcus spp. and Echerichia coli who were admitted in Pusan National University Children's Hospital between January 2010 and January 2013 were included in our study. We retrospectively reviewed their medical records. RESULTS: During the study period, 201 patients were identified to have first episode of community acquired UTIs. 154 cases were E.coli UTIs (76.6%) and 11 cases were enterococcal UTIs (5.5%) and all enterococcus spp. were Enterococcus feacalis. In enterococcal UTI group, voiding cystourethrogram(VCUG) was performed in 7/11 patients and demonstrated 4 vesicoureteral refluxes (VURs) with renal scar and 3 patients underwent corrective surgery. In E.coli UTI group, VCUG was performed in 121/154 patients and demonstrated 23 VURs and 11 patients underwent corrective surgery. Enterococcal group had significant high rate of underlying urinary abnormalities and surgical corrections compared with E. coli group. All enterococcus spp. were susceptible to ampicillin, vancomycin and linezolid, but all were resistant to tetracycline. They also showed 71.4% resistance to trimethoprim-sulfamethoxazole and 20% resistance to ciprofloxacin. CONCLUSION: Community acquired enterococcal UTIs in children were rare within our urban area. However, they could be indicative of severe underlying urinary tract abnormalities.

Recent Advances in Tuberculosis and Nontuberculous Mycobacteria Lung Disease / 결핵및호흡기질환

Tuberculosis (TB) is one of the largest health problems in the world today. And the incidence of nontuberculous mycobacteria (NTM) lung disease appears to be increasing worldwide. Recently, an automated, nucleic acid amplification assay for the rapid detection of both Mycobacterium tuberculosis and rifampin resistance was developed (Xpert MTB/RIF). And fixed-dose combinations of anti-TB drugs and linezolid have been introduced in the treatment of TB. And new NTM species, named Mycobacterium massiliense, which is very closely related to Mycobacterium abscessus was reported. In this review, these recent advances in the diagnosis and treatment of TB and clinical characteristics of M. massiliense lung disease are discussed.

Antimicrobial activity of linezolid combined with minocycline against vancomycin-resistant Enterococci / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Vancomycin-resistant Enterococci (VRE) cause serious infections that are difficult to treat. We carried out this study to determine the mutant prevention concentration (MPC) of linezolid when combined with minocycline against VRE strains, to determine the mechanism of drug resistance in vitro, and to provide a theoretical basis for the rational use of drugs against VRE.</p><p><b>METHODS</b>The minimum inhibitory concentrations (MICs) of linezolid and minocycline against 30 Enterococci (E.) isolates (including 20 VRE strains) were determined by the broth microdilution method. Drug interactions were assessed by the checkerboard microdilution tests and confirmed by time-kill studies. Two vancomycin-susceptible strains N27 and N40 (linezolid MIC, 2 g/ml; minocycline MIC, 4 µg/ml) and control strains E. faecalis ATCC 29212 and ATCC 51299 were also tested. The MPCs of linezolid and minocycline (alone and combined) were determined using the agar dilution method. Strains showing stable resistance were analyzed by polymerase chain reaction (PCR) amplification of domain V of the 23S rRNA gene.</p><p><b>RESULTS</b>Checkerboard titration studies revealed synergistic effects of combination therapy in 26.7% of 30 E. isolates. Antagonism was not observed. The G2576U mutation was detected in stable linezolid-resistant strains of ATCC 29212, N40, and N27 before and after resistance screening, and MIC values increased with the number of G2576U mutations. The MPC of linezolid against E. decreased dramatically when combined with minocycline, and vice versa.</p><p><b>CONCLUSION</b>Linezolid or minocycline alone produce resistant strains; however, their joint use may reduce the MPC of each agent against VRE, thereby decreasing resistant mutants and bacterial infections.</p>

Effects of lovastatin, clomazone and methyl jasmonate treatment on the accumulation of purpurin and mollugin in cell suspension cultures of Rubia cordifolia / 中国天然药物

AIM@#To determine the IPP origin of the naphthoquinones (NQs) in Rubia cordifolia, and to evaluate the effects of methyl jasmonate (MeJA) treatment, MEP, and MVA pathway inhibitor treatment on the accumulation of anthraquinones (AQs) and NQs in cell suspension cultures of R. cordifolia.@*METHODS@#Cell suspension cultures of R. cordifolia were established. Specific inhibitors (lovastatin and clomazone) and MeJA were supplied to the media, respectively. Treated cells were sampled every three days. Content determination of purpurin (AQs) and mollugin (NQs) were carried out using RP-HPLC. The yield of the two compounds was compared with the DMSO-supplied group and the possible mechanism was discussed.@*RESULTS@#Lovastatin treatment increased the yield of purpurin and mollugin significantly. Clomazone treatment resulted in a remarkable decrease of both compounds. In the MeJA-treated cells, the purpurin yield increased, meanwhile, the mollugin yield decreased compared with control.@*CONCLUSION@#The IPP origin of mollugin in R. cordifolia cell suspension cultures was likely from the MEP pathway. To explain the different effects of MeJA on AQs and NQs accumulation, studies on the regulation and expression of the genes, especially after prenylation of 1,4-dihydroxy-2-naphthoic acid should be conducted.

Detection of resistance to linezolid in Staphylococcus aureus infecting orthopedic patients.

Context: In today's medical scenario, the human race is battling the most intelligent enemy who has unending alternatives to combat with the potent elements they have produced against it. Aim: To study the resistance to linezolid among Staphylococcus aureus isolated from pus samples of orthopedic patients. Settings and Design: Pus samples were collected from dirty wounds of orthopedic patients undergoing long antimicrobial treatment programs. The sampling period was from July 2010 to June 2011. The samples were collected from different orthopedic hospitals of Nagpur (central India) representing a mixed sample of patients. Materials and Methods: One hundred pus samples were screened for S. aureus, by growth on mannitol salt agar (MSA), Baird-Parker agar (BPA), deoxyribonuclease test, tube coagulase test, and HiStaph latex agglutination test. Fifty-one S. aureus isolates were obtained which were further subjected to antimicrobial susceptibility testing by Kirby-Bauer disc diffusion method (DDM). Minimal inhibitory concentrations (MICs) were determined by an automated system, the VITEK 2 system. Also, Ezy MIC strip method was carried out in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. Results and Conclusion: Twelve linezolid-resistant S. aureus (LRSA) isolates were recovered from 51 S. aureus cultures tested for susceptibility to linezolid using the DDM, VITEK 2 system, and Ezy MIC strip method. The emergence of resistance suggests nosocomial spread and abuse of antibiotic.

Caracterização molecular dos mecanismos de resistência à linezolida em estafilococos coagulase-negativos e estudo da estabilidade do fenótipo resistente / Linezolid resistance in negative-coagulase staphylococci: characterization and stability of resistant phenotype

Linezolida foi o primeiro fármaco da classe das oxazolidinonas a ser aprovado para o uso clínico. Esta nova oxazolidinona inibe a síntese protéica impedindo a formação do complexo de iniciação formado pelo mRNA, tRNA f-Met e a subunidade 50S do ribossomo bacteriano. Embora a resistência à linezolida possa ser mediada pelo produto do gene cfr ou por mutações nas proteínas ribossômicas L3, L4 e L22, o mecanismo de resistência mais comum envolve mutações no domínio V do gene rRNA 23S. Entre março de 2008 a dezembro de 2011, 38 cepas de estafilococos coagulase-negativos (SCNs) resistentes à linezolida (20 S. epidermidis, 14 S. haemolyticus, 3 S. hominis e 1 S. warneri) isoladas de hemoculturas e pontas de cateter de pacientes internados em dois hospitais terciários do Estado de São Paulo foram incluídas neste estudo para a determinação dos mecanismos de resistência e análise da estabilidade do fenótipo resistente. As cepas de SCNs apresentaram altos níveis de resistência à linezolida (CIMs de 16-128 µg/ml) e foram multi-resistentes, permanecendo sensíveis à vancomicina e teicoplanina. A mutação G2576T foi identificada no domínio V do gene rRNA 23S em todas as cepas de SCNs, exceto em uma cepa de S. haemolyticus. O gene cfr e mutações nas proteínas L4 e L22 não foram detectados. Em relação à proteína L3, todas as cepas de S. epidermidis do hospital A, incluindo a cepa controle sensível à linezolida, apresentaram a substituição Leu101Val, sugerindo que essa mutação seja um marcador clonal dessa população sem envolvimento com a resistência à linezolida. A única cepa proveniente do hospital B (S. epidermidis) foi selvagem para essa proteína ribossômica. Somente uma cepa de S. haemoyticus teve uma mutação no gene rplC, resultando na alteração Val154Leu. Em S. hominis, a mutação Phe147Ile foi identificada em uma cepa, enquanto a associação de Gly139Arg e Met156Thr foi observada nas outras duas cepas dessa espécie. A identificação dessas mutações na proteína L3 de...

Linezolid was the first agent of the oxazolidinone class to be introduced clinically. This oxazolidinone inhibits protein biosynthesis by preventing the formation of the initiation complex that consists of the mRNA, the f-Met tRNA and the 50S subunit of the ribosome. Although linezolid resistance has been mediated by the cfr-encoded product or by ribosomal proteins (L3, L4 and L22), the most common mechanism of resistance involves mutations in the central loop of domain V of the 23S rRNA gene. From March 2008 to December 2011, 38 coagulase-negative staphylococci (CNS) strains (20 S. epidermidis, 14 S. haemolyticus, 3 S. hominis e 1 S. warneri) exhibiting resistance to linezolid were isolated from blood and catheter cultures from patients in two tertiary care hospitals in the State of São Paulo and were included in this study for the ascertainment of the resistance mechanisms to this antimicrobial agent and for the analysis of the stability of this resistance. The strains exhibited high-level resistance to linezolid (MICs 16-128 µg/ml) and all were multidrug resistant, remaining susceptible to vancomycin and teicoplanin. The G2576T mutation in domain V region of 23S rRNA was identified in all isolates, except in a linezolid-resistant S. haemolyticus strain. The cfr gene and mutations in ribosomal proteins L4 and L22 were not detected. Regarding L3 protein analysis, all S. epidermidis strains of hospital A, including the linezolid-susceptible control strain, showed the L3 Leu101Val mutation, suggesting that this alteration is probably not involved in linezolid resistance. The one strain from hospital B (S. epidermidis) was wild-type for this ribosomal protein. Only one S. haemolyticus strain had a mutation in the L3 protein, Val154Leu. Two S. hominis strains showed Gly139Arg/Met156Thr mutations whereas one strain had Phe147Ile in L3 protein. The identification of these mutations in L3 protein of the linezolid-resistant S. haemolyticus and S. hominis strains...

A Case of Septic Arthritis Caused by Persistent MRSA Bacteremia with Successful Treatment Through Linezolid / 감염과화학요법

Vancomycin is the primary antibiotic administered for treatment of methicillin-resistant S. aureus (MRSA) infection; however, treatment failure of vancomycin is currently not uncommon in patients with in vitro vancomycin susceptibile S. aureus (MIC < or = 2 microg/mL) infection. In this report, we describe a case of septic arthritis caused by persistent MRSA bacteremia and treated successfully with linezolid after failure of initial vancomycin therapy.

A Case of Linezolid-Associated Lactic Acidosis / 대한내과학회지

Linezolid has been used for treatment of vancomycin-resistant Enterococcus faecium infection, nosocomial pneumonia caused by Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus or Streptococcus pneumoniae, and complicated and uncomplicated skin and skin structure infections. Lactic acidosis is an adverse effect associated with drugs, including metformin, the nucleoside reverse-transcriptase inhibitors and, rarely, linezolid. We report a case in which severe lactic acidosis developed as an adverse effect of linezolid in a 75-year-old woman who had been on linezolid for 30 days for treatment of a wound infection caused by methicillin-resistant coagulase-negative Staphylococcus. Discontinuation of linezolid and hemodialysis improved her lactic acidosis.