RESUMEN
BACKGROUND: Following the invasion of eukaryotic cells, Salmonella enterica serovar Typhimurium replaces PBP2/PBP3, main targets of ß-lactam antibiotics, with PBP2SAL/PBP3SAL, two homologue peptidoglycan synthases absent in Escherichia coli. PBP3SAL promotes pathogen cell division in acidic environments independently of PBP3 and shows low affinity for ß-lactams that bind to PBP3 such as aztreonam, cefepime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime and cefalotin. OBJECTIVES: To find compounds with high affinity for PBP3SAL to control Salmonella intracellular infections. METHODS: An S. Typhimurium ΔPBP3 mutant that divides using PBP3SAL and its parental wild-type strain, were exposed to a library of 1520 approved drugs in acidified (pH 4.6) nutrient-rich LB medium. Changes in optical density associated with cell filamentation, a read-out of blockage in cell division, were monitored. Compounds causing filamentation in the ΔPBP3 mutant but not in wild-type strain-the latter strain expressing both PBP3 and PBP3SAL in LB pH 4.6-were selected for further study. The bactericidal effect due to PBP3SAL inhibition was evaluated in vitro using a bacterial infection model of cultured fibroblasts. RESULTS: The cephalosporin cefotiam exhibited higher affinity for PBP3SAL than for PBP3 in bacteria growing in acidified LB pH 4.6 medium. Cefotiam also proved to be effective against intracellular Salmonella in a PBP3SAL-dependent manner. Conversely, cefuroxime, which has higher affinity for PBP3, showed decreased effectiveness in killing intracellular Salmonella. CONCLUSIONS: Antibiotics with affinity for PBP3SAL, like the cephalosporin cefotiam, have therapeutic value for treating Salmonella intracellular infections.
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Antibacterianos , Proteínas Bacterianas , Cefuroxima , Células Eucariotas , Proteínas de Unión a las Penicilinas , Salmonella typhimurium , Antibacterianos/farmacología , Antibacterianos/metabolismo , Proteínas Bacterianas/metabolismo , Cefotiam/metabolismo , Cefotiam/farmacología , Ceftazidima/farmacología , Cefuroxima/farmacología , Cefalosporinas/farmacología , Cefalosporinas/metabolismo , Escherichia coli , Células Eucariotas/efectos de los fármacos , Células Eucariotas/metabolismo , Monobactamas/farmacología , Proteínas de Unión a las Penicilinas/genética , Proteínas de Unión a las Penicilinas/metabolismo , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismoRESUMEN
RATIONALE: Antibiotics can cause central nervous system disturbances, manifesting as dizziness, confusion, headache, and seizures. Seizures due to antibiotic administration are related to increased excitatory neurotransmission because antibiotics act as competitive antagonists of the γ-aminobutyric acid type A receptor. PATIENT CONCERNS AND CLINICAL FINDINGS: All 5 patients, comprising 4 females and one male and aged 45 to 72 years, underwent open craniotomy with additional surgical maneuvers according to their specific disease. All patients presented American Society of Anesthesiologists Physical Status grades 1 to 2. There were no specific underlying diseases, except hepatitis C and hypertension. However, seizures developed sequentially in the 5 patients after neurosurgery. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Early postcraniotomy seizures (PCS) developed in the patients after neurosurgery. Prophylactic antibiotics were administered in all cases to prevent infection due to open craniotomy. This included the administration of 10 g and 2 g of an antibiotic (cefotiam HCL; Jetiam Intravenous Injection 1g®) an hour before the surgery in the ward and half an hour before the surgery in the operating room, respectively. After surgery, cefotiam HCL 2 g was administered in all patients on the day of surgery. Five patients had myoclonic seizure or generalized tonic-clonic seizure several times at emergence or in the intensive care unit. LESSONS: Early PCS occurred in every patient when an overdose of the prophylactic antibiotic was administered. This report showed that the preoperative prophylactic antibiotic cefotiam administered in double doses evoked early PCS within a few hours of drug administration. Furthermore, such experiences caution that preoperative intravenous cephalosporins, including cefotiam, should be administered carefully in open craniotomy.
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Neurocirugia , Femenino , Humanos , Masculino , Cefotiam , Procedimientos Neuroquirúrgicos , Convulsiones/etiología , Antibacterianos/uso terapéuticoRESUMEN
OBJECTIVES: In March 2019, cefazolin was unavailable owing to difficulty in procuring the active ingredient. Furthermore, the supply of alternative drugs, such as cefotiam and cefmetazole, was limited. In the Department of Nephro-Urology, fosfomycin-based drugs are used as substitutes for cefazolin, which is a perioperative prophylactic antibacterial drug. Herein, we investigated the effectiveness of fosfomycin sodium and cefotiam in preventing infection after endoscopic combined intrarenal surgery as a retrospective preliminary study. METHODS: A total of 200 patients who underwent endoscopic combined intrarenal surgery at our department between August 2017 and January 2021 were included. The patients were administered cefotiam (n = 95) or fosfomycin (n = 105) as perioperative antibacterial agents. There were no significant differences in the median age or surgery time between the cefotiam and fosfomycin groups. Propensity score matching was performed to match the preoperative urine bacterial counts of both groups. Sixty-eight patients were selected from each group. RESULTS: The median postoperative hospital stay duration was 4 days for the two groups. The median maximum postoperative temperatures were 37.5 and 37.4°C, respectively. There were no significant differences between the maximum postoperative temperatures in both groups. Furthermore, there were no differences between the groups regarding the white blood cell counts, C-reactive protein levels, and aspartate aminotransferase and alanine aminotransferase levels postoperatively, as well as in terms of postoperative fever requiring additional antibiotics. CONCLUSIONS: During a period of difficulty in acquiring cefazolin and cefotiam, the use of fosfomycin allowed us to continue with the procedure without increased clinical complications.
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Fosfomicina , Antibacterianos/uso terapéutico , Cefazolina/uso terapéutico , Cefotiam , Fosfomicina/uso terapéutico , Humanos , Estudios RetrospectivosRESUMEN
In the current study, we used 7922 FDA approved small molecule drugs as well as compounds in clinical investigation from NIH's NPC database in our drug repurposing study. SARS-CoV-2 main protease as well as Spike protein/ACE2 targets were used in virtual screening and top-100 compounds from each docking simulations were considered initially in short molecular dynamics (MD) simulations and their average binding energies were calculated by MM/GBSA method. Promising hit compounds selected based on average MM/GBSA scores were then used in long MD simulations. Based on these numerical calculations following compounds were found as hit inhibitors for the SARS-CoV-2 main protease: Pinokalant, terlakiren, ritonavir, cefotiam, telinavir, rotigaptide, and cefpiramide. In addition, following 3 compounds were identified as inhibitors for Spike/ACE2: Denopamine, bometolol, and rotigaptide. In order to verify the predictions of in silico analyses, 4 compounds (ritonavir, rotigaptide, cefotiam, and cefpiramide) for the main protease and 2 compounds (rotigaptide and denopamine) for the Spike/ACE2 interactions were tested by inâ vitro experiments. While the concentration-dependent inhibition of the ritonavir, rotigaptide, and cefotiam was observed for the main protease; denopamine was effective at the inhibition of Spike/ACE2 binding.
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Antivirales , Reposicionamiento de Medicamentos , Drogas en Investigación/farmacología , SARS-CoV-2/efectos de los fármacos , Enzima Convertidora de Angiotensina 2 , Antivirales/farmacología , Cefotiam/farmacología , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Evaluación Preclínica de Medicamentos , Humanos , Simulación del Acoplamiento Molecular , Ritonavir/farmacología , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Tratamiento Farmacológico de COVID-19RESUMEN
INTRODUCTION: In March 2019, cefazolin availability was limited owing to the contamination of the drug substance. In addition, there was a difficulty in supplying drugs alternative to cefazolin, such as cefotiam and cefmetazole. In our Department of Nephro-urology, we used fosfomycin-based drugs to substitute cefazolin as perioperative preventive antibacterial drugs. In this study, we aimed to evaluate the usage status of perioperative prophylactic antibacterial drugs before and after the period of limited cefazolin supply and to investigate the efficacy and safety of fosfomycin sodium in preventing infections following transurethral resection of bladder tumor. METHODS: We enrolled 346 patients who underwent transurethral resection of bladder tumor in our department from April 2018 to August 2020. The patients received the following perioperative antibacterial agents: cefotiam (n = 146), fosfomycin (n = 166), and other antibacterial agents (n = 34). There was no significant difference in the median age or surgery time. RESULTS: The median length of hospital stay was 6, 5, and 5 days in the cefotiam, fosfomycin, and other antibacterial groups, respectively, with significant difference. The median maximum postoperative temperature was 37.1 °C in all groups, with no significant difference. There were no differences in C-reactive protein, aspartate aminotransferase, and alanine aminotransferase levels determined by postoperative blood tests; preoperative and postoperative urinary white blood cell counts; preoperative urine bacterial counts; and surgery-related infection requiring additional antibiotic treatments among the groups. CONCLUSIONS: The use of fosfomycin-based agents helped overcome the limited supply of cefazolin without worsening clinical outcomes.
Asunto(s)
Fosfomicina , Neoplasias de la Vejiga Urinaria , Antibacterianos/uso terapéutico , Cefazolina/uso terapéutico , Cefmetazol/uso terapéutico , Cefotiam , Fosfomicina/uso terapéutico , Humanos , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
Bacteremia is often caused by gram-negative bacteria (represented by EKP; Escherichia coli, Klebsiella species, and Proteus mirabilis), and the excessive use of cefazolin, as the first-line antimicrobial in its treatment, has been a source of concern in the emergence of resistant strains. As an antimicrobial, cefotiam may be an alternative to cefazolin; however, little evidence is available for its use in the treatment of bacteremia. The purpose of this non-inferiority study was to retrospectively compare the therapeutic efficacy of cefotiam with some antimicrobials of narrow spectrum (cefazolin, cefmetazole, and flomoxef) in the treatment of EKP-induced bacteremia. The number of patients recruited was 32 in the cefotiam group and 29 in the control group. In the primary endpoint, the survival rate on day 28 for the cefotiam group and the control group was 93.5% and 89.3%, respectively (relative risk at day 28, 1.048; 95% confidence interval, 0.894-1.227). In the secondary end point, treatment success rate in the two groups was 71.9% and 69.0%, respectively (relative risk, 1.042; 95% confidence interval, 0.752-1.445). Intensive care unit admission, low body weight, hypoalbuminemia, and infections unassociated with the urinary tract were identified to be the risk factors responsible for treatment failure. We demonstrated cefotiam may be non-inferior to other antimicrobials of similar spectrum, in terms of survival rate, in EKP-induced bacteremia.
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Bacteriemia , Proteus mirabilis , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Cefotiam , Escherichia coli , Humanos , Klebsiella , Estudios RetrospectivosRESUMEN
BACKGROUND: Cefotiam, a second-generation cephalosporin, is a broad-spectrum antibiotic with good antibacterial action against both gram-negative and gram-positive bacteria. It is used widely in clinical practice, although bacterial drug resistance makes its clinical use problematic. The authors hypothesized that subtherapeutic concentrations of cefotiam leads to bacterial resistance. The present study was conducted to evaluate whether the standard cefotiam dosing regimen resulted in a subtherapeutic concentrations in children. METHOD: Data were prospectively collected from pediatric patients with suspected or confirmed community-acquired pneumonia who were receiving cefotiam at the standard dosing regimen (40-80 mg/kg, 2 or 3 times daily). A blood sample was collected after 70%-100% of the dosing interval, and plasma concentrations were determined by high-performance liquid chromatography using an ultraviolet detector. RESULTS: The data from 88 patients (age, 3.0 ± 2.8 years; weight, 15.4 ± 8.3 kg) were used for analysis. The average of cefotiam concentrations was 0.06 mcg/mL (range: <0.05-0.79 mcg/mL). Most patients (n = 72, 81.8%) had concentrations below 0.1 mcg/mL; only 2 patients had concentrations higher than 0.4 mcg/mL. CONCLUSIONS: The standard dosing regimen for cefotiam resulted in extremely low plasma concentrations in children; such low concentrations may lead to antimicrobial drug resistance. Thus, an increase in cefotiam dosage in children to 80 mg/kg 4 times daily is recommended (maximum dose on the label).
Asunto(s)
Antibacterianos/uso terapéutico , Cefotiam/uso terapéutico , Adolescente , Infecciones Bacterianas/tratamiento farmacológico , Niño , Preescolar , Farmacorresistencia Microbiana/efectos de los fármacos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: Tissue adhesive injection is the first-line treatment for gastric varices rebleeding. Available studies are focused on antibiotic usage in emergency endoscopy, while the use of antibiotics in selective endoscopic tissue adhesive treatment remains controversial. METHODS: This is a randomized controlled study conducted in a tertiary referral hospital. Consecutive patients were enrolled from February 16, 2016, to November 19, 2016, and blindly randomized into two treatment groups. Patients in the prophylactic group received 2 g of cefotiam during endoscopic injection of tissue adhesive. All the subjects were observed for rebleeding, fever, and changes in laboratory indicators in hospital and post-discharge. RESULT: One hundred and seven patients who received endoscopic therapy for gastroesophageal varices were included. Fifty-three patients were allocated to the antibiotic prophylactic group and 54 patients to the on-demand group. The two groups had similar baseline characteristics. The incidence of fever in hospital was 2/53 (3.8%) vs 9/54 (16.7%) (P = 0.028). Perioperative and postoperative clinical events were significantly lower in the antibiotic prophylactic group (5.7% vs 24.1%, P = 0.018; 7.5% vs 20.4%, P = 0.050). Inflammation indices were elevated on the first day after endoscopic therapy; however, no significant difference was observed between the two groups. The cumulative rebleeding free rate within 2 months was lower in the antibiotic prophylactic group (1.9% vs 9.3%, P = 0.100). CONCLUSION: Our study illustrated that prophylactic use of antibiotics in selective endoscopic injection of tissue adhesive reduced the incidence of the total clinical events in perioperative period and had a trend towards lower rebleeding in 2 months.
Asunto(s)
Antibacterianos/administración & dosificación , Profilaxis Antibiótica , Cefotiam/administración & dosificación , Endoscopía Gastrointestinal , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Hemostasis Endoscópica , Adhesivos Tisulares/administración & dosificación , Adulto , Anciano , Antibacterianos/efectos adversos , Profilaxis Antibiótica/efectos adversos , Cefotiam/efectos adversos , China , Endoscopía Gastrointestinal/efectos adversos , Femenino , Fiebre/etiología , Hemostasis Endoscópica/efectos adversos , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Proyectos Piloto , Recurrencia , Factores de Tiempo , Adhesivos Tisulares/efectos adversos , Resultado del TratamientoRESUMEN
Two structural isomers of cefotiam in cefotiam hydrochloride for injection were observed, and the structures of the isomers were determined by mass spectrometry and various 1D and 2D NMR techniques. The thermo-isomerization mechanism of cefotiam was also discussed. Thermo-isomerization occurred not only in cefotiam but also in cephalosporins containing a 1-alkyl-1H-tetrazole-5-thiol side chain at C-3. Furthermore, the toxic effects of the two impurities of cefotiam hydrochloride were predicted and it is thought that they could be more toxic than cefotiam. The results reported in this article may be important for quality control and stability studies of this class of drugs.
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Antibacterianos/análisis , Cefotiam/análisis , Cefalosporinas/análisis , Contaminación de Medicamentos/prevención & control , Control de Calidad , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/toxicidad , Cefotiam/química , Cefotiam/aislamiento & purificación , Cefotiam/toxicidad , Cefalosporinas/química , Cefalosporinas/aislamiento & purificación , Cefalosporinas/toxicidad , Química Farmacéutica , Simulación por Computador , Estabilidad de Medicamentos , Isomerismo , Espectroscopía de Resonancia Magnética/instrumentación , Espectroscopía de Resonancia Magnética/métodos , Espectrometría de Masas/instrumentación , Espectrometría de Masas/métodos , Simulación del Acoplamiento Molecular , TemperaturaRESUMEN
A 26-year-old woman presented with recurrent attacks of widespread urticaria and systemic symptoms. The patient was a nurse, and the attacks occurred only in her workplace, without an apparent trigger. A patch test to cefotiam (CTM) induced an immediate skin reaction. ELISA detected the patient's serum IgE antibody binding to CTM conjugated with human serum albumin (CTM-HSA), and her basophils released histamine in response to CTM-HSA in a histamine release assay (HRA). Both reactions in ELISA and HRA were inhibited by pretreatment of the patient's serum or basophils with cefotiam. No crossreactivity in skin tests or in vitro assays was observed against other antibiotics, even those containing a beta-lactam ring and/or side chains similar to CTM. Certain antibiotics including CTM may cause extremely sensitive and specific contact urticaria syndrome, which is mediated by IgE and evoked even without apparent skin contact with the culprit drug and in the absence of any history of an allergic reaction against other antibiotics with similar structures.
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Cefotiam/inmunología , Inmunoglobulina E/inmunología , Enfermedades Profesionales/inducido químicamente , Urticaria/inducido químicamente , Adulto , Cefotiam/efectos adversos , Femenino , Humanos , Personal de Enfermería en Hospital , Enfermedades Profesionales/inmunología , Urticaria/inmunologíaRESUMEN
Routine perioperative intravenous antimicrobial agents are administered as surgical prophylaxis. However, whether balanced ultrafiltration during extracorporeal circulation has substantial effect on the concentration of antimicrobial agents remains unclear. The concentrations of antimicrobial agents in plasma and ultrafiltrate samples were measured in this pseudo-extracorporeal circulation model. Extracorporeal circulation consisted of cardiotomy reservoir, membrane oxygenator, and pediatric arterial line filter. A hemoconcentrator was placed between the arterial purge line and oxygenator venous reservoir. Fresh donor human whole blood was added into the circuit and mixed with Ringer's solution to obtain a final hematocrit of 24-28%. Two kinds of antimicrobial agents, cefotiam (320 mg) and cefmetazole (160 mg), were bolus added into the circuit. After 30 min of extracorporeal circulation, zero-balanced ultrafiltration was initiated and arterial line pressure was maintained at approximately 100 mm Hg with a Hoffman clamp. The rate of ultrafiltration (12 mL/min) was controlled by ultrafiltrate outlet pressure. An identical volume of Plasmalyte A was dripped into the circuit to maintain stable hematocrit during 45 min of experiment. Plasma and ultrafiltrate samples were drawn every 5 min, and concentrations of antimicrobial agents (including cefotiam and cefmetazole) were measured with high performance liquid chromatography. Both antimicrobial agents were detected in ultrafiltrate, demonstrating hemoconcentration may remove antimicrobial agents. The concentrations of plasma antimicrobial agents decreased linearly with the increase of ultrafiltrate volume. At end of balanced ultrafiltration, the concentration of plasma cefotiam was 104.96 ± 44.36 mg/L, which is about 44.38% ± 7.42% of the initial concentration (238.95 ± 101.12 mg/L) (P < 0.001); the concentration of plasma cefmetazole decreased linearly to 25.76 ± 14.78 mg/L, which is about 49.69% ± 10.49% of the initial concentration (51.49 ± 28.03 mg/L) (P < 0.001). The total amount of cefotiam in ultrafiltrate is 27.16% ± 12.17% of the total dose administered, whereas cefmetazole in ultrafiltrate is 7.74% ± 4.17%. Balanced ultrafiltration may remove antimicrobial agents from plasma and has a prominent influence on plasma concentration of antimicrobial agent. The strategy of surgical prophylaxis should consider this unique technique during extracorporeal circulation.
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Antiinfecciosos/sangre , Cefmetazol/sangre , Cefotiam/sangre , Circulación Extracorporea/instrumentación , Ultrafiltración/instrumentación , Diseño de Equipo , Hemodinámica , HumanosAsunto(s)
Infecciones por Salmonella/diagnóstico , Salmonella/aislamiento & purificación , Antibacterianos/uso terapéutico , Cefotaxima/uso terapéutico , Cefotiam/uso terapéutico , Humanos , Lactante , Masculino , República de Corea/epidemiología , Infecciones por Salmonella/tratamiento farmacológico , Infecciones por Salmonella/epidemiologíaRESUMEN
OBJECTIVE: To detect unknown impurities in raw drug material of cefotiam hexetil. METHODS: High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was employed for the determination of impurities in cefotiam hexetil. Agilent SB-C18 column (150 mm x 2.1 mm i. d. , 3.5 microm particles) was used for chromatographic separations of cofotiam hexetil dissolved in deionized water, with mobile phase consisting of (A) 0.1% formic acid and (B) acetonitrile and timed gradient program T (min)/B (%): 0/3, 5/3, 15/20, 20/40, 30/60, 40/80. The flow rate was set at 0. 3 mL/min with DAD detector wavelength fixed at 254 nm. Electrospray ionization source was applied and operated in positive ion MRM mode. The source voltage was kept at 4 kV and cone voltage was 100 V with the mass range m/z 50-1000. Nitrogen was used as nebulizing gas and the nebulizer pressure was 40 psi. The drying gas temperature was 350 degrees C and the drying gas flow was 10 L/min. Results Unknown impurities of cefotiam hexetil were identified. Substance 1 was delta3-isomer of cefotiam hexetil. The structures of 3 other substances were also determined. CONCLUSION: The method is sensitive, rapid and credible for the analysis of cefotiam hexetil and its related impurities, which can be applied in quality control of cefotiam hexetil.
Asunto(s)
Cefotiam/análogos & derivados , Cromatografía Líquida de Alta Presión , Contaminación de Medicamentos , Espectrometría de Masas en Tándem , Cefotiam/química , Contaminación de Medicamentos/prevención & control , Control de CalidadRESUMEN
Kingella species including K. kingae are non-motile coccobacilli or short straight rods, and their normal habitats appear to be the upper respiratory and oropharyngeal tracts of humans. In recent years, K. kingae strains have been increasingly recognized as common causes of invasive infections in children at the age of less than 4 years. In Japan, however, invasive K. kingae infections including osteomyelitis have rarely been described. We incidentally encountered isolation of a K. kingae strain from intraoperatively obtained specimens from a previously healthy 44-month-old boy. He first consulted a nearby medical facility and a suspected diagnosis of osteomyelitis was made, after which the patient was then transferred to our Nagano Children's hospital. There was evidence of inflammation in his right calcaneus and toe walking was noted. He was treated with surgical drainage. An isolate grown on sheep blood agar with positive oxidase and negative catalase was biochemically characterized with the ID-Test HN20 (Nissui Pharmaceutical Co., Ltd., Tokyo, Japan) kit system together with genetic examinations involving sequencing the 16S rRNA gene, and the infection was finally identified as K. kingae. The patient was successfully treated with cefotiam (CTM) for the first 7 days followed by the administration of trimethoprim-sulfamethoxazole (ST) for an additional 2 months. The K. kingae isolate was confirmed as a sure causative pathogen by observing that the serum showed high agglutinin titers against the isolate. Accumulation of the case reports in Japan with the isolation of this species is essential for clarifying invasive infections due to K. kingae. Our case report is a noteworthy and useful piece of information.
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Tobillo/patología , Artritis Infecciosa/tratamiento farmacológico , Cefotiam/uso terapéutico , Kingella kingae/aislamiento & purificación , Osteomielitis/tratamiento farmacológico , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Artritis Infecciosa/diagnóstico , Preescolar , Humanos , Japón , Masculino , Osteomielitis/diagnóstico , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of this study was to investigate the hypothesis that prevention of surgical site infection (SSI) is equally effective when patients receive single-dose (SD) or three-dose antibiotic prophylaxis with second-generation cephalosporin and metronidazole in elective colorectal surgery. METHODS: Ninety-three patients were enrolled from May 2009 to November 2010. The SD group received only one preoperative prophylactic intravenous dose and the three-dose or multiple-dose (MD) group received one preoperative prophylactic and two additional post-operative doses of second-generation cephalosporin and metronidazole. The incidence of infectious complications (SSI of the incision site and organ/space) was compared in the two groups. RESULTS: The overall post-operative infection rate did not differ between the two groups (16.7% in the SD versus 13.3% in the MD, P = 0.653). The incidence of SSI of the incision site and organ/space also did not differ between the groups (6.3% (3/48) versus 4.4% (2/45), P = 0.700; 4.2% versus 6.7%, P = 0.593, respectively). The number of antibiotics administered was not an independent risk factor for SSIs in multivariable analysis. CONCLUSIONS: SD antibiotic prophylaxis with second-generation cephalosporin and metronidazole is equivalent to a three-dose prophylaxis for preventing SSI in elective colorectal surgery. But further study would be needed to clarify this because of the small number of participants.
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Antibacterianos/administración & dosificación , Profilaxis Antibiótica/métodos , Cefotiam/administración & dosificación , Colectomía , Metronidazol/administración & dosificación , Recto/cirugía , Infección de la Herida Quirúrgica/prevención & control , Administración Intravenosa , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Cefotiam/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Incidencia , Masculino , Metronidazol/uso terapéutico , Persona de Mediana Edad , Cuidados Posoperatorios/métodos , Cuidados Preoperatorios/métodos , Modelos de Riesgos Proporcionales , Factores de Riesgo , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Resultado del TratamientoRESUMEN
Pneumatosis intestinalis (PI) is a comparatively rare disease characterized by the presence of intramural gas in the gastrointestinal tract. PI is known to be associated with several clinical conditions, such as pulmonary diseases, gastrointestinal diseases, and traumatic injury, as well as autoimmune disorders. In particular, PI is commonly seen in systemic sclerosis (SSc) but rarely in systemic lupus erythematosus and dermatomyositis (DM). In this report, we present three cases of PI presenting in autoimmune diseases, including DM, Sjögren's syndrome, and limited SSc, and further discuss its background characteristics.
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Enfermedades Autoinmunes/diagnóstico , Dermatomiositis/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Neumatosis Cistoide Intestinal/diagnóstico , Esclerodermia Sistémica/diagnóstico , Adulto , Antibacterianos/uso terapéutico , Enfermedades Autoinmunes/complicaciones , Cefotiam/uso terapéutico , Colostomía , Terapia Combinada , Dermatomiositis/complicaciones , Diagnóstico Diferencial , Resultado Fatal , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Persona de Mediana Edad , Terapia Nutricional , Neumatosis Cistoide Intestinal/complicaciones , Neumatosis Cistoide Intestinal/terapia , Inducción de Remisión , Esclerodermia Sistémica/complicaciones , Tomografía Computarizada por Rayos XRESUMEN
ß-Lactam antibiotics have cerebral and peripheral adverse effects. Multidrug resistance-associated protein 4 (MRP4) has been reported to transport several ß-lactam antibiotics, and its expression at the blood-brain barrier also serves to limit their distribution to the brain. Therefore, the purpose of this study was to clarify the structure-activity relationship of MRP4-mediated transport of ß-lactam antibiotics using MRP4-expressing Sf9 membrane vesicles. The transport activity was evaluated as MRP4-mediated transport per MRP4 protein [nL/(min·fmol MRP4 protein)] based on measurement of MRP4 protein expression by means of liquid chromatography-tandem mass spectrometry. Cefotiam showed the greatest MRP4-mediated transport activity [8.90 nL/(min·fmol MRP4 protein)] among the ß-lactam antibiotics examined in this study. Measurements of differential transport activity of MRP4 for various ß-lactam antibiotics indicated that (i) cephalosporins were transported via MRP4 at a greater rate than were penams, ß-lactamase inhibitors, penems, or monobactams; (ii) MRP4-mediated transport activity of anionic cephalosporins was greater than that of zwitterionic cephalosporins; and (iii) higher-molecular-weight anionic ß-lactam antibiotics showed greater MRP4-mediated transport activity than lower-molecular-weight ones, whereas zwitterionic ß-lactam antibiotics did not show molecular weight dependency of MRP4-mediated transport. These quantitative data should prove useful for understanding MRP-related adverse effects of ß-lactam antibiotics and their derivatives.
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Antibacterianos/química , Antibacterianos/farmacocinética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , beta-Lactamas/química , beta-Lactamas/metabolismo , Transporte Biológico , Barrera Hematoencefálica/metabolismo , Cefotiam/metabolismo , Humanos , Peso Molecular , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/biosíntesis , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Relación Estructura-ActividadRESUMEN
An adequate protocol for antimicrobial prophylaxis (AMP) in radical prostatectomy (RP) has not been established. We retrospectively compared the occurrence of perioperative infection following RP between two different AMP protocols. This study included 340 cases with prostate cancer who underwent RP at our institution between January 2005 and December 2008. The 1-day group consisting of 93 cases received a second generation cephem, cefotiam, intravenously during and after the operation on the operative day. The single dose group consisting of 247 cases received cefotiam during the operation only. The incidence of surgical site infection (SSI) and remote infection (RI) was retrospectively investigated. There was no significant difference in the rate of SSI and RI occurrence between the 1-day group (2.2, 0%) and single dose group (3.6, 0.4%) (p = 0.52). The single dose protocol of AMP seems sufficient for prevention of perioperative infection in RP.
Asunto(s)
Infecciones Bacterianas/prevención & control , Cefotiam/administración & dosificación , Prostatectomía , Anciano , Humanos , Masculino , Complicaciones Posoperatorias/prevención & control , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
We report a case of severe "bodybuilding acne" in a 22-year-old patient. Treatment with isotretinoin paradoxically led to exaceibation and occurrence of pyogenic granuloma-like lesions.