RESUMEN
BACKGROUND: Although Streptococcus agalactiae is the leading causative agent of neonatal sepsis and meningitis, recently it is increasingly isolated from non-pregnant adults. The relation between its presence in the genitourinary tract and manifested clinical symptoms of STD patients remains an open question. In this study, a complex epidemiological investigation of GBS isolates from a venerology clinic was performed. METHODS: Ninety-six GBS isolates were serotyped and their genetic relatedness determined by PFGE. MLST was also performed for a subset of 20 isolates. The antibiotic susceptibility was tested with agar dilution. Surface proteins and the ST-17 hypervirulent clone was detected by PCR. RESULTS: The serotype prevalence was the following: V (29.2%), III (27.1%), Ia (22.9%), IV (10.4%), II (5.2%) and Ib (4.2%). A strong association was demonstrated between surface protein genes and serotypes. All isolates were fully susceptible to penicillin, but erythromycin and clindamycin resistance was high (41.7 and 35.4%, respectively), and 8 phenotypically macrolide sensitive isolates carried the ermB gene. 21.9% of all strains belonged to the hypervirulent ST17 clone, most being of serotype III and all were rib +. We found a few serotype IV isolates belonging to several STs and one serotype V/ST110 strain, containing a 44-bp deletion in the atr allele. CONCLUSIONS: The presence of silent ermB genes is of worry, as their expression upon macrolide exposure could lead to unforeseen therapeutic failure, while clindamycin is used for intrapartum antibiotic prophylaxis, in case of penicillin allergy. The other alarming result is the high prevalence of ST17 among these strains from STD patients, who could be sources of further infections. This is the first report from Hungary providing both serotyping and genotyping data of GBS isolates. These results could be helpful for vaccine production as the major vaccine candidates are capsular antigens or surface proteins.
Asunto(s)
Infecciones Estreptocócicas/diagnóstico , Streptococcus agalactiae/genética , Adulto , Antibacterianos/farmacología , Proteínas Bacterianas/genética , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Farmacorresistencia Bacteriana/efectos de los fármacos , Femenino , Humanos , Hungría/epidemiología , Macrólidos/farmacología , Pruebas de Sensibilidad Microbiana , Fenotipo , Prevalencia , Serogrupo , Infecciones Estreptocócicas/epidemiología , Streptococcus agalactiae/efectos de los fármacos , Streptococcus agalactiae/aislamiento & purificación , Streptococcus agalactiae/patogenicidad , Virulencia/genéticaRESUMEN
In order to obtain new, cluster-forming antibiotic compounds, teicoplanin pseudoaglycone derivatives containing two lipophilic n-octyl chains have been synthesized. The compounds proved to be poor antibacterials, but, surprisingly, they exhibited potent anti-influenza virus activity against influenza A strains. This antiviral action was related to inhibition of the binding interaction between the virus and the host cell. Related analogs bearing methyl substituents in lieu of the octyl chains, displayed no anti-influenza virus activity. Hence, an interaction between the active, dually n-octylated compounds and the lipid bilayer of the host cell can be postulated, to explain the observed inhibition of influenza virus attachment.
Asunto(s)
Antivirales/farmacología , Orthomyxoviridae/efectos de los fármacos , Teicoplanina/farmacología , Animales , Antivirales/síntesis química , Antivirales/química , Sitios de Unión/efectos de los fármacos , Perros , Relación Dosis-Respuesta a Droga , Membrana Dobles de Lípidos/metabolismo , Células de Riñón Canino Madin Darby/efectos de los fármacos , Células de Riñón Canino Madin Darby/metabolismo , Células de Riñón Canino Madin Darby/virología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad , Teicoplanina/síntesis química , Teicoplanina/químicaRESUMEN
The high mortality of patients with coronavirus disease 2019 (COVID-19) is effectively reduced by vaccination. However, the effect of vaccination on mortality among hospitalised patients is under-researched. Thus, we investigated the effect of a full primary or an additional booster vaccination on in-hospital mortality among patients hospitalised with COVID-19 during the delta wave of the pandemic. This retrospective cohort included all patients (n = 430) admitted with COVID-19 at Semmelweis University Department of Medicine and Oncology in 01/OCT/2021-15/DEC/2021. Logistic regression models were built with COVID-19-associated in-hospital/30 day-mortality as outcome with hierarchical entry of predictors of vaccination, vaccination status, measures of disease severity, and chronic comorbidities. Deceased COVID-19 patients were older and presented more frequently with cardiac complications, chronic kidney disease, and active malignancy, as well as higher levels of inflammatory markers, serum creatinine, and lower albumin compared to surviving patients (all p < 0.05). However, the rates of vaccination were similar (52-55%) in both groups. Based on the fully adjusted model, there was a linear decrease of mortality from no/incomplete vaccination (ref) through full primary (OR 0.69, 95% CI: 0.39-1.23) to booster vaccination (OR 0.31, 95% CI 0.13-0.72, p = 0.006). Although unadjusted mortality was similar among vaccinated and unvaccinated patients, this was explained by differences in comorbidities and disease severity. In adjusted models, a full primary and especially a booster vaccination improved survival of patients hospitalised with COVID-19 during the delta wave of the pandemic. Our findings may improve the quality of patient provider discussions at the time of admission.
Asunto(s)
COVID-19 , Pandemias , Humanos , Hungría/epidemiología , Vacunas contra la COVID-19 , Estudios Retrospectivos , COVID-19/epidemiología , VacunaciónRESUMEN
The primary amino function of teicoplanin pseudoaglycon has been transformed into arylthioisoindole or benzoisoindole and glycosylthioisoindole derivatives, in a reaction with o-phthalaldehyde or naphtalene-2,3-dicarbaldehyde and various thiols. All of the obtained semisynthetic antibiotics exhibited potent antibacterial activities against Gram-positive bacteria in the ng per ml concentration range. A few of them showed antiviral activity, in particular against influenza virus.
Asunto(s)
Antibacterianos/síntesis química , Antivirales/síntesis química , Isoindoles/química , Teicoplanina/química , Antibacterianos/química , Antibacterianos/farmacología , Antivirales/farmacología , Antivirales/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Farmacorresistencia Viral/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Herpesvirus Humano 1/efectos de los fármacos , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza B/efectos de los fármacos , Isoindoles/síntesis química , Pruebas de Sensibilidad Microbiana , o-Ftalaldehído/químicaRESUMEN
UNLABELLED: Ureaplasma urealyticum and Mycoplasma hominis have important role among the causative agents of sexually transmitted diseases. AIM: The aim of the study was to determine the frequency and antibiotic resistance of Ureaplasma urealyticum and Mycoplasma hominis in genital samples obtained from patients examined in the Sexually Transmitted Diseases Centre of the Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, Budapest between May 1, 2008 and July 31, 2010. PATIENTS AND METHODS: Samples were taken from the urethra in men and from the cervix and urethra in women by universal swab (Biolab®) into Urea-Myco DUO kit (Bio-Rad®) and were incubated for 48 hours at 37 C°. Antibiotic sensitivity of positive samples was determined in U9 bouillon using SIR Mycoplasma kit (Bio-Rad®). RESULTS: Samples for 4154 patients aged 16-60 years were examined. In 247/4154 samples (6%) U. urealyticum and in 26/4154 samples (0.63%) M. hominis was isolated from the genital tract. Most U. urealyticum and M. hominis strains (75% and 77%, respectively) were cultured from cervix, while the remaining 25%, and 23% from the male and female urethra, respectively. U. urealyticum and M. hominis were most commonly detected in patients aged between 21 and 40 years. The majority of U. urealyticum strains were sensitive to tetracycline (94%), doxycycline (95%), azithromycin (88%) and josamycin (90%), but were resistant to ofloxacin (21%), erythromycin (85%) and clindamycin (79%). Seventy-seven percent of the U. urealyticum strains were simultaneously resistant to erythromycin and clindamycin, suggesting that ex iuvantibus therapies may select cross-resistant strains to both antibiotics. The resistance of M. hominis to clindamycin, doxycycline, ofloxacin and tetracycline varied between 4% and 12 %. CONCLUSIONS: Because none of the strains was sensitive to all examined antibiotics, the antibiotic sensitivity of U. urealyticum and M. hominis strains should be determined. The high rate of ofloxacin, erythromycin and clindamycin resistance should be considered in the therapy of U. urealyticum infections in Hungary. This is the first such a clinical microbiological study in this topic in Hungary.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Mycoplasma hominis/efectos de los fármacos , Conducta Sexual , Enfermedades Bacterianas de Transmisión Sexual/tratamiento farmacológico , Ureaplasma urealyticum/efectos de los fármacos , Sistema Urogenital/microbiología , Adolescente , Adulto , Clindamicina/farmacología , Eritromicina/farmacología , Femenino , Humanos , Hungría , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycoplasma hominis/aislamiento & purificación , Ofloxacino/farmacología , Enfermedades Bacterianas de Transmisión Sexual/diagnóstico , Enfermedades Bacterianas de Transmisión Sexual/microbiología , Ureaplasma urealyticum/aislamiento & purificaciónRESUMEN
OBJECTIVES: The designer antibacterial peptide A3-APO is efficacious in mouse models of Escherichia coli and Acinetobacter baumannii systemic infections. Here we compare the efficacy of the peptide with that of imipenem and colistin in A. baumannii wound infections after burn injury. METHODS: CD-1 mice were inflicted with burn wounds and different inocula of A. baumannii, isolated from an injured soldier, were placed into the wound sites. The antibiotics were given intramuscularly (im) one to five times. Available free peptide in the blood and the systemic toxicity of colistin and A3-APO were studied in healthy mice. RESULTS: While toxicity of colistin was observed at 25 mg/kg bolus drug administration, the lowest toxic dose of A3-APO was 75 mg/kg. In the A. baumannii blast injury models, 5 mg/kg A3-APO improved survival and reduced bacterial counts in the blood as well as in the wounds and improved wound appearance significantly better than any other antibiotic treatment. The free peptide concentration in the blood did not reach 1 µg/mL. CONCLUSIONS: Peptide A3-APO, with an intramuscular therapeutic index of 15, is more efficacious and less toxic than any existing burn injury infection therapy modality against multidrug-resistant Gram-negative pathogens. A3-APO administered by the im route probably binds to a biopolymer that promotes the peptide's biodistribution.
Asunto(s)
Infecciones por Acinetobacter/tratamiento farmacológico , Antibacterianos/administración & dosificación , Quemaduras/complicaciones , Péptidos/administración & dosificación , Infección de Heridas/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , Animales , Antibacterianos/farmacocinética , Colistina/administración & dosificación , Colistina/efectos adversos , Colistina/farmacocinética , Modelos Animales de Enfermedad , Femenino , Humanos , Imipenem/administración & dosificación , Imipenem/efectos adversos , Imipenem/farmacocinética , Inyecciones Intramusculares , Ratones , Péptidos/efectos adversos , Péptidos/farmacocinética , Plasma/química , Resultado del Tratamiento , Infección de Heridas/microbiologíaRESUMEN
New sugar derivatives of ristocetin were prepared by copper-catalyzed 1,3-dipolar cycloaddition reaction using azido-ristocetin aglycon and various propargyl glycosides. Some of them were found to be active against gram-positive bacteria and showed favorable antiviral activity against the H1N1 subtype of influenza A virus.
Asunto(s)
Antibacterianos/síntesis química , Antivirales/síntesis química , Doxorrubicina/análogos & derivados , Ristocetina/análogos & derivados , Antibacterianos/química , Antibacterianos/farmacología , Antivirales/química , Antivirales/farmacología , Catálisis , Cobre/química , Doxorrubicina/química , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Ristocetina/síntesis química , Ristocetina/farmacologíaRESUMEN
Nosocomial infections are the main cause of extra charges in health care and they relate to patient safety, as well. About 30 percent of healthcare-associated infections can be prevented effectively with infection control and adequate screening methods. Currently, meticillin-resistant Staphylococcus aureus is the main nosocomial pathogen. Protective measures against this bacterium are well known, therefore it was selected for our present cost /benefit analysis. We have calculated the costs of the epidemic caused by methicillin-resistant Staphylococcus aureus at the Aladar Petz County Teaching Hospital, Gyor, in a two-year period, and also calculated the costs of the screening method. We compared our results with the published data. Screening methods are much less expensive than to cure the patient of a nosocomial infection. Thus, primary prevention has essential importance.
Asunto(s)
Infección Hospitalaria/economía , Brotes de Enfermedades/economía , Costos de la Atención en Salud , Hospitales de Enseñanza/economía , Control de Infecciones/economía , Tamizaje Masivo/economía , Tamizaje Masivo/métodos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/economía , Adulto , Anciano , Análisis Costo-Beneficio , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Femenino , Hospitales de Enseñanza/estadística & datos numéricos , Humanos , Incidencia , Control de Infecciones/métodos , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Prevención Primaria/economía , Prevención Primaria/métodos , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/prevención & controlRESUMEN
Összefoglaló. Az élelmiszer-eredetu megbetegedések igen gyakoriak, bár pontos adatok nem állnak rendelkezésre, mivel az enyhe, gyorsan múló gastrointestinalis tünetekkel a betegek nem fordulnak orvoshoz, vagy nem történik diagnosztikus vizsgálat. Az amerikai Járványügyi és Betegségmegelozési Központ (CDC) adatai szerint az USA-ban évente 6 lakosból 1 esik át élelmiszer okozta tüneteken. Az ételintoxikációk során a baktérium által termelt toxinok okozzák a tüneteket, közülük a leggyakoribb a Clostridium perfringens, a Staphylococcus aureus és a Bacillus cereus okozta, élelmiszer-eredetu intoxikáció. A nem megfeleloen tárolt vagy hokezelt élelmiszerekben - beleértve a S. aureus által szennyezett anyatejet - ezen baktériumok életképesek maradnak, elszaporodnak, és toxint termelhetnek, illetve toxinjaik megorzik megbetegítoképességüket. Az étel elfogyasztása után 3-12 órával hányást, hasmenést okoznak. A tünetek többnyire 24 órán belül megszunnek. A Clostridium botulinum súlyos neurológiai tünetei miatt emelkedik ki a többi toxikoinfekció sorából. C. botulinum okozta tünetekre felnotteknél házi készítésu konzervek és húskészítmények elfogyasztása után jelentkezo gastrointestinalis vagy neurológiai tünetek esetén kell gondolnunk. A Clostridioides difficile szintén a toxinjai révén okoz súlyos, életveszélyes megbetegedést, továbbá az esetek 20-30%-ában számolnunk kell az infekció relapsusával. Növekvo gyakorisága miatt ismernünk érdemes a laboratóriumi és klinikai diagnosztika részleteit és a legmodernebb kezelési lehetoségeket, úgymint megfelelo mintavétel, mintatárolás és -szállítás, tenyésztés, toxinkimutatás, helyes tüneti kezelés, antibiotikumkombinációk, széklettranszplantáció és monoklonálisantitest-kezelés. Orv Hetil. 2020; 161(48): 2019-2028. Summary. Foodborne diseases are quite common, however, accurate data are not available because patients do not visit doctors with mild, rapidly resolving symptoms and diagnostic tests are not performed. The Centers of Disease Control and Prevention (CDC) estimates that, in the USA, 1 in 6 citizens gets food poisoning yearly. Symptoms of intoxication are due to the toxins produced by bacteria, mostly by Clostridium perfringens, Staphylococcus aureus and Bacillus cereus. These bacteria can survive in not properly stored or heated food, including S. aureus contaminated breastmilk. They can multiply and produce toxins causing intoxications. The gastrointestinal symptoms start 3-12 hours after consumption of the contaminated food and resolve in 24 hours. Clostridium botulinum causes severe neurological symptoms that should be suspected after consumption of home-made cans, smoked hams and sausages. The disease caused by Clostridioides difficile is not a foodborne one, but C. difficile causes severe infection via its toxins. Another problem is that C. difficile infection recurs in 20-30% of cases. Due to the increasing incidence of foodborne diseases, it is worth to learn the precise clinical and laboratory diagnostic algorithms including sampling, storage and transportation of samples, cultivation of bacteria and differential diagnosis of these diseases, furthermore the most up-to-date symptomatic and causative treatment options like antibiotic combinations, stool transplantation and monoclonal antibodies. Orv Hetil. 2020; 161(48): 2019-2028.
Asunto(s)
Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/tratamiento farmacológico , Clostridioides difficile/aislamiento & purificación , Clostridium botulinum/aislamiento & purificación , Clostridium perfringens/aislamiento & purificación , Enfermedades Transmitidas por los Alimentos/diagnóstico , Enfermedades Transmitidas por los Alimentos/tratamiento farmacológico , Staphylococcus aureus/aislamiento & purificación , Antibacterianos/uso terapéutico , Infecciones Bacterianas/microbiología , Enfermedades Transmitidas por los Alimentos/microbiología , HumanosRESUMEN
Cytotoxin genes in 128 Austrian (AT) MSSA, 48 MRSA, 94 Hungarian (HU) MSSA, 110 MRSA and 67 Macedonian (MK) MSSA, 81 MRSA strains were examined. The presence of alfa-haemolysin gene (hla) was more common in HU MSSA strains compared to AT and MK (99%, 86%, 72%: p<0.001). AT and MK MRSA harboured hlb genes more frequently compared to HU (60%, 62%, 33%: p<0.001). HU and MK MRSA strains carried gamma-haemolysin gene (hlg) in higher percentage in contrast to AT (88%, 83%, 69%: p=0.01). Haemolysin gamma-variant gene (hlgv) was more prevalent in HU MSSA compared to AT and MK (84%, 56%, 69%: p<0.001). Panton-Valentine leukocidin genes were found only in AT, HU, MK MSSA and MK MRSA in 2.3%, 4%, 1.5% (p=0.53) and 1% (p=0.38), respectively. The 3-gene combination pattern comprising of hla, hlg and hld genes showed increased prevalence among AT MSSA compared to HU (27%, 11%: p<0.001). The 4-gene pattern composed of hla, hlg, hlgv and hld genes was significantly characteristic for HU MRSA in contrast to AT and MK MRSA (56%, 12.5%, 27%: p<0.001). Frequency of certain cytotoxin genes and combinations differed significantly in Staphylococcus aureus strains according to geographical origin and methicillin-resistance.
Asunto(s)
Citotoxinas/genética , Proteínas Hemolisinas/genética , Leucocidinas/genética , Resistencia a la Meticilina , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/genética , Austria , Humanos , Hungría , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , República de Macedonia del Norte , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
The STD Department of Semmelweis University Budapest is the National Centre of Hungary, which is responsible for screening and care of sexually transmitted diseases (STD), including syphilis and gonorrhoea. 42,114 patients attended the STD Department and 25,362 anonymous screening (HIV: 12,337, syphilis: 13,025) were done between January 2005 and December 2008. During this period 600 syphilitic and 339 gonorrhoea infections were diagnosed. The obligatory HIV screening of patients with sexually transmitted infections (STI) resulted positive result in 47 cases, and 63 patients infected with HIV acquired new syphilitic or gonorrhoea infection. Contact tracing was successful in around 400 syphilis cases, and 150-200 gonorrhoea cases per year. We present our statistical data in order to call attention to the resurgence of syphilis and gonorrhoea and the importance of STD co-infections.
Asunto(s)
Trazado de Contacto , Gonorrea/diagnóstico , Gonorrea/epidemiología , Sífilis/diagnóstico , Sífilis/epidemiología , Adolescente , Adulto , Anciano , Comorbilidad , Femenino , Gonorrea/transmisión , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Humanos , Hungría/epidemiología , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Sífilis/transmisión , Serodiagnóstico de la Sífilis , Universidades , Adulto JovenRESUMEN
The presence of the vanA gene was determined in enterococci from healthy poultry, originating from the Hungarian resistance monitoring system between 2001 and 2004. Enterococci (n = 562) were collected from intestinal samples of slaughtered broiler chickens. The presence of van genes was detected by polymerase chain reaction (PCR). The vancomycin-resistant enterococcus (VRE) strains carried only the vanA gene. Genus- and species-level identification of the vanA gene carrier strains was carried out by PCR using specific primers. In 2001, 25 out of the 289 isolated strains (8.6%) were vanA carriers (1 Enterococcus mundtii, 13 E. durans and 11 E.faecium). In 2002 (n = 87), 20 (23%) strains were vanA positive (11 E. durans and 9 E. faecium). In 2003 and 2004, none of the strains (n = 95 and 91, respectively) were positive for the most common van genes. In 2003, there was only one strain for which higher minimum inhibitory concentrations (MIC) of vancomycin (4 mg/L) and teicoplanin (8 mg/L) were found. In 2004 there were three strains for which the MIC of vancomycin was 8 mg/L, and 2 strains and 1 strain with teicoplanin MICs of 4 mg/L and 8 mg/L, respectively. The potential similarity of these strains was studied by pulsed-field gel electrophoresis (PFGE). The VRE strains were not closely related to one another. The annual data of vancomycin resistance indicate an association between the recovery of vancomycin-resistant enterococci and the use of avoparcin in animal feeds. This study indicates that with the reduced use of antibiotics in food animals, it is possible to decrease the rate of resistant bacteria. Although the use of avoparcin had been banned in 1998, the VRE strains disappeared only five years later.
Asunto(s)
Pollos/microbiología , Enterococcus/efectos de los fármacos , Resistencia a la Vancomicina/fisiología , Vancomicina/farmacología , Animales , Enterococcus/genética , Hungría/epidemiología , Pruebas de Sensibilidad Microbiana , FilogeniaRESUMEN
In vitro and in vivo activities of amikacin and imipenem alone, and in combination, were studied against an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain. The strain was in vitro susceptible to both antimicrobials at 10(5) and 10(7) CFU/mL. In time-kill studies amikacin, imipenem, and amikacin plus imipenem decreased the bacterial counts; difference between the bactericidal effects was not observed. Chequerboard technique showed no interaction between the tested drugs. Mice infected with 10(7) CFU/g of the K. pneumoniae were treated by amikacin (15 mg/kg every 8 h), imipenem (40 mg/kg every 4 h), or amikacin plus imipenem for 24 h. Blood bacterial counts in the group treated with amikacin plus imipenem did not differ significantly from the groups treated with amikacin or imipenem alone. Combination of amikacin and imipenem did not demonstrate any advantage over imipenem alone either in vitro or in vivo.
Asunto(s)
Amicacina/farmacología , Antibacterianos/farmacología , Imipenem/farmacología , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/efectos de los fármacos , beta-Lactamasas/biosíntesis , Amicacina/farmacocinética , Amicacina/uso terapéutico , Animales , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Imipenem/farmacocinética , Imipenem/uso terapéutico , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/enzimología , Masculino , Ratones , Pruebas de Sensibilidad MicrobianaRESUMEN
Interleukin-1 receptor-associated kinase (IRAK)-4 deficiency is a rare primary immunodeficiency disorder characterized by severe, invasive infections with Streptococcus pneumoniae. Using the PFGE technique a genetic linkage was found between two S. pneumoniae serotype 14 isolates causing arthritis and meningitis at 3 and 5(1/2) years of age, respectively, in a boy with IRAK-4 deficiency. This finding suggested that patients with IRAK-4 deficiency may harbour persistent strains of pneumococci. Alternatively, reinfection with strains from close contacts of the patient might cause recurrent invasive disease. It is proposed that eradication of pneumococci from the nasopharynx, and immunization of household contacts may prevent recurrent infection in IRAK-4-deficient patients.
Asunto(s)
Quinasas Asociadas a Receptores de Interleucina-1/deficiencia , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae/aislamiento & purificación , Artritis/microbiología , Niño , Dermatoglifia del ADN , ADN Bacteriano/genética , Electroforesis en Gel de Campo Pulsado , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Quinasas Asociadas a Receptores de Interleucina-1/inmunología , Masculino , Meningitis/microbiología , Epidemiología Molecular , Infecciones Neumocócicas/inmunología , Recurrencia , Serotipificación , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/genéticaRESUMEN
The water-soluble N-methoxy-PEG-yl-, N-beta-D-glucopyranosyl- and N-beta-D-maltosylthioureido aglyco-ristocetin were prepared which, in contrast to ristocetin A, did not induce thrombocyte aggregation. The antibacterial activity of N-beta-D-maltosylthioureido aglyco-ristocetin A against MRSA was comparable to that of ristocetin A, while its activity against Enterococcus faecalis (VRE, TSE) is somewhat stronger when compared to those of vancomycin and ristocetin A.
Asunto(s)
Agregación Plaquetaria/efectos de los fármacos , Ristocetina/farmacología , Bacterias/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Ristocetina/síntesis química , Ristocetina/químicaRESUMEN
The aglycones of the antibiotics eremomycin, vancomycin and ristocetin (3, 4 and 6, respectively) were prepared by deglycosidation of the parent antibiotics with hydrogen fluoride, and complete assignation of their 1H, 13C and 15N spectra was performed. The squaric acid amide esters (11-14), were prepared from dimethyl squarate. The corresponding asymmetric diamides (16-19, 22, 23) were also synthesized using 4-phenylbenzylamine and triglycine. The advantage of the method is the high regioselectivity and that no protecting group strategy is required. Electrospray mass spectroscopic method was elaborated for the determination of the site of substitution of the modified antibiotics. The antibacterial activity of the prepared compounds is discussed in detail.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Glicopéptidos/química , Glicopéptidos/farmacología , Antibacterianos/síntesis química , Enterococcus faecalis/efectos de los fármacos , Glicopéptidos/síntesis química , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Ristocetina/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Vancomicina/químicaRESUMEN
The simulation of human serum levels is essential in animal models to extrapolate the experimental results to clinical practice. Administration of a nephrotoxic drug such as cisplatin can be used to cause renal dysfunction as an approach to mimic human serum levels of renally excreted drugs. We aimed to determine the dose of cisplatin that did not affect the survival rate of mice and to achieve human-like serum concentrations of cefepime. Different doses of cisplatin (0, 10, 14, 18, 22 and 26 mg/kg) were given by intraperitoneal (i.p.) injection to mice three days prior to the i.p. administration of 80 mg/kg cefepime. With cisplatin doses of 18 and 22 mg/kg, the half-life of cefepime was significantly prolonged (P < 0.001) and all mice survived. The pretreatment with 26 mg/kg cisplatin significantly decreased survival (P = 0.001), but the half-life of cefepime was not significantly longer than of 18 mg/kg cisplatin. Serum levels of cefepime after the pretreatment with 18 mg/kg cisplatin were comparable to published human data. The administration of cisplatin appears to be a suitable method in mice for simulating human serum concentrations of renally excreted drugs.
Asunto(s)
Animales de Laboratorio/metabolismo , Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Cisplatino/farmacología , Enfermedades Renales/inducido químicamente , Ratones/metabolismo , Animales , Animales de Laboratorio/sangre , Antibacterianos/sangre , Área Bajo la Curva , Cefepima , Cefalosporinas/sangre , Interacciones Farmacológicas , Semivida , Masculino , Ratones/sangre , Modelos Animales , Estadísticas no ParamétricasRESUMEN
The macrolide resistance of 304 Hungarian Streptococcus pneumoniae isolates was investigated. Antibiotic sensitivity testing was performed in air and in 5% CO(2). More erythromycin resistance was noted when growth was in CO(2). A resistance determinant was found in almost all isolates: erm(B) gene (87.4%), mef genes (9.2%) and one strain with the erm(TR) gene. This indicates that screening for carriage of resistance determinants should always be done in the presence of 5% CO(2). We found three isolates with mef(E), which were highly resistant to erythromycin. These contained multiple and some novel, ribosomal mutations. The most prevalent serogroups were 6, 19 and 14. Based on the PFGE pattern, we found identity between the Hungarian isolates and two PMEN clones.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/genética , Farmacorresistencia Bacteriana/genética , Macrólidos/farmacología , Proteínas de la Membrana/genética , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Dermatoglifia del ADN , ADN Bacteriano/genética , Electroforesis en Gel de Campo Pulsado , Genes Bacterianos , Genes de ARNr/genética , Humanos , Hungría , Metiltransferasas/genética , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Mutación , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
Thirty-five clinical isolates of coagulase-negative staphylococci with decreased glycopeptide sensitivity were examined by a penicillin-binding protein (PBP2') latex agglutination (LA) test and were compared to the detection of the mecA gene by PCR, and oxacillin susceptibility determined minimum inhibitory concentrations. The latex test demonstrated high sensitivity and specificity for detecting methicillin resistance in coagulase-negative staphylococci after PBP2' induction with oxacillin.
Asunto(s)
Antiinfecciosos/farmacología , Resistencia a la Meticilina/fisiología , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus haemolyticus/efectos de los fármacos , Teicoplanina/farmacología , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Ligasas de Carbono-Oxígeno/química , Ligasas de Carbono-Oxígeno/genética , ADN Bacteriano/química , ADN Bacteriano/genética , Electroforesis en Gel de Campo Pulsado , Humanos , Pruebas de Fijación de Látex/métodos , Pruebas de Sensibilidad Microbiana , Proteínas de Unión a las Penicilinas/química , Reacción en Cadena de la Polimerasa , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/metabolismo , Staphylococcus haemolyticus/genética , Staphylococcus haemolyticus/metabolismoRESUMEN
Despite the close structural similarity between the heptapeptide cores of the glycopeptide antibiotics teicoplanin and ristocetin, synthetically modified derivatives of their aglycons show significantly different antibacterial and antiviral properties. The teicoplanin aglycon derivatives with one exception proved to be potent antibacterials but they did not exhibit anti-influenza virus activity. In contrast, the aglycoristocetin derivatives generally showed high anti-influenza virus activity and possessed moderate antibacterial activity. A systematic structure-activity relationship study has been carried out on ristocetin and teicoplanin aglycon derivatives, to explore which structural differences are responsible for these markedly different biological activities. According to electronic circular dichroism and in silico conformational studies, it was found that the differences in anti-influenza virus activity are mainly determined by the conformation of the heptapeptide core of the antibiotics controlled by the presence or absence of chloro substituents. Knowledge of the bioactive conformation will help to design new analogs with improved anti-influenza virus activity. For the teicoplanin derivatives, it was shown that derivatization to improve the antiviral efficacy was accompanied by a significant decrease in antibacterial activity.