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Biomedical subjects

A Fleer

Publications and source records attributed to A Fleer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Oral antibiotics as a novel therapy for arthritis: evidence for a beneficial effect of intestinal Escherichia coli.

OBJECTIVE: The intestinal flora is thought to play an important role in regulation of immune responses. We investigated the effects of changing the intestinal flora on the course of adjuvant-induced arthritis (AIA) and on experimental autoimmune encephalomyelitis (EAE) by the use of oral antibiotics. METHODS: Oral treatment with either vancomycin or vancomycin, tobramycin, and colistin was started after AIA and EAE induction. Clinical symptoms of AIA and EAE were monitored, and microbial analysis of ileal samples was performed. RESULTS: Oral vancomycin treatment after disease induction significantly decreased clinical symptoms of AIA. Simultaneously, increased concentrations of Escherichia coli were detected in the distal ileum of vancomycin-treated rats. Ileal concentrations of E coli were inversely related to disease scores in rats with AIA. Coadministration of colistin/tobramycin to prevent the increase in E coli abrogated the beneficial effect of vancomycin on AIA. Vancomycin treatment also reduced the clinical symptoms of EAE. CONCLUSION: We propose oral vancomycin as a novel therapeutic strategy in autoimmune diseases.

Administration, Oral↗
PubMed2000

Effects of hydrosyapatite coating on Ti-6A1-4V implant-site infection in a rabbit tibial model.

To investigate the effect of implant type after direct contamination, a hydroxyapatite-coated or noncoated Ti-6A1-4V implant was inserted into both tibiae of 32 New Zealand White rabbits. Prior to implantation, the left tibia was contaminated with increasing concentrations of Staphylococcus aureus (10(2)-10(5) colony-forming units), ranging from very low (10(2)) to relatively high (10(5)). Four weeks after implantation, half of the tibial bone adjacent to the implant was harvested for bacteriological examination. Bacterial counts were quantified by plating serial dilutions. For the histological evaluation, sections of the implant with the remaining tibia were examined by semiquantitative scoring of infection parameters. The bacteriological data showed the inoculum dose and implant type to have a significant effect on the culture outcome: more bacteria were retrieved from the hydroxyapatite-coated implants than from the noncoated titanium implants. Histological evaluation showed an increased score for the infected left tibiae compared with their contralateral control. In addition, with increasing inoculum dosage, the difference between the two types of implant increased. We demonstrated that infections can occur with biocompatible, noncemented implants and that they are related to the dose of the original inoculum. Bacteria were more likely to grow onto or next to the hydroxyapatite implants than on titanium implants and resulted in a more severe histopathological characterization of infection.

Aluminum↗
PubMed2000

Severe neonatal group A streptococcal disease.

UNLABELLED: Since the mid-1980s, an increase in incidence of invasive disease caused by group A streptococci has been noted amongst adults and children; however, neonatal disease is still rare. Between 1979 and 1998, seven neonates with severe group A streptococcal disease were admitted to our neonatal intensive care unit. The clinical presentation, treatment and outcome are described. In three cases of early-onset disease vertical transmission was documented. CONCLUSION: Because the incidence of group A streptococcal disease in the general population seems to have increased over the last two decades, we should be aware of the possibility and particularly the severity of group A streptococcal disease in the neonatal period.

Female↗
PubMed2000

Cellular and humoral defence mechanisms against bacteria.

Host defence to bacterial infection is a complex process of highly efficient effector systems that co-operate to eliminate microbial invaders. The systems not only co-operate, they are also interdependent, as deficiency of one system may cause dysfunction in another. As is so often the case in medicine, the discovery of the various effector systems and their components originated from studies of patients with unusually severe, frequently recurring infections. Modern molecular biology has greatly aided in elucidation of the basic disorders and identification of the corresponding gene defect. This knowledge will hopefully provide us with better tools for causal therapy in the future; at present the only available "cure" is bone marrow transplantation, a treatment modality with many problems of its own.

Antibody Formation↗
PubMed2000

Molecular epidemiology of penicillin-resistant Streptococcus pneumoniae colonizing children with community-acquired pneumonia and children attending day-care centres in Fortaleza, Brazil.

To study clonal diversity of penicillin-resistant Streptococcus pneumoniae, 161 randomly selected isolates with reduced susceptibility to penicillin, collected from the nasopharynx of children under 5 years of age with community-acquired pneumonia and healthy controls from public day-care and immunization centres in Fortaleza, Brazil, were characterized by microbiological and serological techniques and automated ribotyping. Also included were 44 randomly selected penicillin-susceptible strains and three international reference strains. With automated ribotyping 75 ribopatterns were observed: 50 ribogroups were unique and 25 ribogroups were represented by two or more isolates. Genetic diversity was extensive but some degree of genetic homogeneity was found in strains from children with pneumonia, strains from children in day-care centres, isolates with reduced susceptibility to penicillin and isolates expressing 'paediatric' serogroups. Fourteen (56%) clusters contained both isolates with reduced penicillin susceptibility and penicillin-susceptible isolates, suggesting emergence of penicillin resistance. In general, there was a good correlation between ribogroups and serogroups, but 12 (48%) clusters contained isolates with alternative serogroups. Isolates with such alternative serogroups were more often encountered in penicillin-susceptible strains (41%) than in strains with reduced susceptibility to penicillin (7%). Thirty-eight (19%) isolates (including seven penicillin-susceptible strains) showed ribotypes indistinguishable from those of two international epidemic clones of S. pneumoniae: ribogroup 54-S-1 (15 isolates) with a ribopattern characteristic of the 23F multiresistant 'Spanish/USA' clone and ribogroup 74-S-3 (23 isolates) with a pattern similar to that of the 6B multiresistant 'Spanish' clone.

Analysis of Variance↗
PubMed1999

Lethal encephalopathy complicating childhood shigellosis.

UNLABELLED: A 6-year-old girl is described who died following rapid neurological deterioration, ending in lethal cerebral oedema. Despite the absence of severe intestinal and metabolic derangement, Shigella was cultured from the stool. Toxic encephalopathy is responsible for death following this rare complication of childhood shigellosis in developed countries. The pathophysiology is unknown. CONCLUSION: Lethal toxic encephalopathy can be caused by Shigella despite the absence of severe intestinal and metabolic derangement. If shigelllosis is suspected, headache may be a first significant sign for the development of toxic encephalopathy. Early recognition and rapid measures to prevent brain oedema may improve outcome.

Bacteremia↗
PubMed1999

Striking differences in the nasopharyngeal flora of healthy Angolan, Brazilian and Dutch children less than 5 years old.

Community-acquired pneumonia from enteric gram-negative bacilli is more common in developing than in industrialized countries. We investigated the nasopharyngeal flora in healthy children from Angola, Brazil and The Netherlands to see whether enteric gram-negative bacilli are more often part of the commensal flora in developing countries. Nasopharyngeal specimens were collected from children aged between 4 months and 5 years in day-care centres and immunization clinics. Children who had received antibiotics or were malnourished were excluded. Brazilian and Angolan children had a higher number of household members than Dutch children (5.5 and 7 vs 3.9 mean number of household members, respectively) (p < 0.0001). Enteric and non-fermentative gram-negative bacilli were much more prevalent in Brazilian (50%) and Angolan (57%) children than in Dutch (4%) children (p < 0.0001). By univariate analysis, carriage of enteric gram-negative bacilli was associated with the number of household members (r = 0.26; p < 0.001). The high carriage rate of enteric gram-negative bacilli in children from Angola and Brazil may explain why enteric gram-negative bacilli are a common cause of pneumonia in developing countries.

Angola↗
PubMed1999

Population pharmacokinetics of gentamicin in preterm neonates: evaluation of a once-daily dosage regimen.

Population pharmacokinetic parameters of gentamicin in preterm neonates on a once-daily dosage regimen of 3.0 mg/kg given intravenously every 24 hours were established prospectively. In 34 preterm neonates with a mean gestational age of 32 +/- 4 (SD), 182 serum gentamicin levels (91 peak/trough pairs) were determined. Individual adjustments of dose or dosage interval were calculated by computer-aided Bayesian forecasting. The parameters Vd, ke, and CL for each patient were obtained by the nonparametric estimation of maximization method. The predictive power of the model was calculated and the pharmacokinetic estimates were statistically analyzed with SPSS/PC. Cluster analysis showed a division into 2 subpopulations (designated 1 and 2) on the basis of postnatal age. The mean +/- SD postnatal age of subpopulation 1 (n = 29) was 6 +/- 2 days (range 1-7) and of subpopulation 2 (n = 5) 15 +/- 4 days (range 12-24). The mean +/- SD gentamicin relative clearances of subpopulation 1 and subpopulation 2 were 0.0515 +/- 0.0128 and 0.1026 +/- 0.0102 L kg(-1) hr(-1), respectively (p < 0.05). The mean +/- SD values for Vd (Lkg(-1)) in both populations 1 and 2 were 0.6916 +/- 0.1670 and 0.7509 +/- 0.1961, respectively (not significantly different). For ke these data were 0.0744 +/- 0.0200 and 0.1366 +/- 0.0522 (p < 0.05). Statistics showed that the data for Vd and ke of subpopulation 1 were normally distributed (Vd and ke skewness 1.61 and 1.46; kurtosis 3.09 and 3.10 respectively). The model yielded a bias of -0.11 mg/L and a precision of 0.36 mg/L. It is recommended that gentamicin be started in a dosage of 3.5 mg/kg intravenously once-daily under close monitoring.

Age Factors↗
PubMed1999

Respiratory viral infection predisposing for bacterial disease: a concise review.

Although bacterial superinfection in viral respiratory disease is a clinically well documented phenomenon, the pathogenic mechanisms are still poorly understood. Recent studies have revealed some of the mechanisms involved. Physical damage to respiratory cells as a result of viral infection may lead to opportunistic adherence of bacteria. Enhanced bacterial adherence by specific mechanisms has been documented for respiratory cells infected with influenza A virus, respiratory syncytial virus and adenovirus in both in vitro and in vivo models. To date, results of various experimental studies indicate that different mechanisms for increased bacterial adherence induced by viruses are operating for specific viral-bacterial combinations. In the present review, a number of key findings obtained during the past two decades is presented and discussed.

Animals↗
PubMed1999

Resistance to both complement activation and phagocytosis in type 3 pneumococci is mediated by the binding of complement regulatory protein factor H.

To study the role of surface-associated proteins in the virulence of Streptococcus pneumoniae, we used two serotype 3 strains, ATCC 6303 and WU2, and two PspA-negative mutants of WU2, an encapsulated one, JY1123 (Caps(+)/PspA(-)), and an unencapsulated one, DW3.8 (Caps(-)/PspA(-)). ATCC 6303 and WU2 were highly virulent in mice, while the virulence of JY1123 was slightly decreased (50% lethal doses [LD(50)s], 24, 6, and 147 CFU/mouse, respectively); DW3.8 was avirulent (LD(50), 2 x 10(8) CFU). In vitro, ATCC 6303, WU2, and JY1123 (Caps(+)/PspA(-)) strongly resisted complement activation and complement-dependent opsonophagocytosis, whereas DW3.8 (Caps(-)/PspA(-)) was easily phagocytized in fresh serum. Trypsin treatment of ATCC 6303, WU2, and JY1123 (Caps(+)/PspA(-)) resulted in enhanced complement activation and complement-dependent opsonophagocytosis. Trypsin had no deleterious effect on the polysaccharide capsule. In addition, trypsin pretreatment of ATCC 6303 strongly reduced virulence upon intraperitoneal challenge in mice. This indicated that surface proteins play a role in the resistance to complement activation and opsonophagocytosis and contribute to the virulence of type 3 pneumococci. In subsequent experiments, we could show that the modulation of complement activation was associated with surface components that bind complement regulator factor H; binding is trypsin sensitive and independent of prior complement activation. Immunoblotting of cell wall proteins of the virulent strain ATCC 6303 with anti-human factor H antibody revealed three factor H-binding proteins of 88, 150, and 196 kDa. Immunogold electron microscopy showed a close association of factor H-binding components with the outer surface of the cell wall. The role of these factor H-binding surface proteins in the virulence of pneumococci is interesting and warrants further investigation.

Animals↗
PubMed1999

Clinical outcome of cephalothin versus vancomycin therapy in the treatment of coagulase-negative staphylococcal septicemia in neonates: relation to methicillin resistance and mec A gene carriage of blood isolates.

OBJECTIVE: Coagulase-negative staphylococci (CONS) are the most common causative agents in neonatal nosocomial septicemia. Because of widespread methicillin resistance among CONS, empiric therapy with vancomycin is recommended as the primary antibiotic regimen for these infections. In our unit, empiric treatment of nosocomially acquired septicemia consists of cephalothin and gentamicin, which are adjusted subsequently according to the determined bacterial susceptibility profile. Vancomycin is initiated only when the patient has been treated recently with cephalothin or when intravascular lines or endotracheal tube are colonized with oxacillin/cephalothin-resistant CONS strains. The aim of the present study was to evaluate the efficacy of our antibiotic regimen for CONS septicemia, in relation to methicillin-resistance and the carriage of mec A gene, encoding methicillin resistance, among CONS blood isolates from our unit. METHODS: Clinical symptoms of septicemia, clinical outcome, and laboratory parameters of septicemia (C-reactive protein) were studied retrospectively in 66 patients with CONS septicemia. The diagnosis of septicemia was made by the attending neonatologist and was defined by clinical symptoms of septicemia in the presence of a positive finding of a blood culture test, which was performed using a defined protocol. All CONS blood isolates were included to determine mec A gene carriage. RESULTS: In the 66 patients, three treatment categories were distinguished: treatment with cephalothin (25 patients, 38%); with vancomycin (15 patients, 23%); and primary treatment with cephalothin, switched subsequently to vancomycin (26 patients, 39%). It was found that 92% of all CONS blood isolates (61/66) were mec A-positive. Concordance of mec A gene carriage with methicillin/oxacillin resistance was found in 56 of 66 isolates (85%); 10 of 61 (16%) isolates that were mec A-positive were determined as oxacillin-susceptible. Although 22 of the 25 blood isolates of the cephalothin-treated patients were mec A-positive, clinical recovery was uneventful. In the 26 patients in whom antibiotic therapy was switched from cephalothin to vancomycin, two strains were cephalothin-susceptible and 8 patients already had recovered clinically before the switch, which was based solely on susceptibility test results. CONCLUSIONS: Cephalothin was found to be clinically efficacious in the treatment of neonatal CONS septicemia, despite a steadily increasing mec A gene carriage of CONS blood isolates in our neonatal intensive care unit and a corresponding high methicillin/oxacillin resistance. Hence, cephalothin remained the antibiotic of first choice in the treatment of CONS septicemia in our unit, with vancomycin selected exclusively for cases not responding to initial cephalothin treatment, or for patients developing CONS septicemia during or after recent cephalothin treatment. By applying this approach in our unit, we were able to reduce vancomycin use from 62% in 1994 to 1995 to 21% in 1997. This shows that such a policy may result in an important reduction of vancomycin use, which may aid in postponing the threatening emergence of vancomycin resistance among Gram-positive cocci.

Anti-Bacterial Agents↗
PubMed1998

Persistence of clones of coagulase-negative staphylococci among premature neonates in neonatal intensive care units: two-center study of bacterial genotyping and patient risk factors.

From 1 January 1995 until 1 January 1996, we studied the molecular epidemiology of blood isolates of coagulase-negative staphylococci (CoNS) in the Neonatal Intensive Care Units (NICUs) of the Sophia Children's Hospital (SCH; Rotterdam, The Netherlands) and the Wilhelmina Children's Hospital (WCH; Utrecht, The Netherlands). The main goal of the present study was to detect putatively endemic clones of CoNS persisting in these NICUs. Pulsed-field gel electrophoresis was used to detect the possible presence of endemic clones of clinical significance. In addition, clinical data of patients in the SCH were analyzed retrospectively to identify risk factors for the acquisition of positive blood cultures. In both centers, endemic CoNS clones were persistently present. Thirty-three percent of the bacterial isolates derived from blood cultures in the SCH belonged to a single genotype. In the WCH, 45% of all bacterial strains belonged to a single clone. These clones were clearly different from each other, which implies that site specificity is involved. Interestingly, we observe that the clonal type in the SCH differed significantly from the incidentally occurring strains with respect to both the average pH and partial CO2 pressure of the patient's blood at the time of bacterial culture. We found that the use of intravascular catheters, low gestational age, and a long hospital stay were important risk factors for the development of a putative CoNS infection. When the antibiotic susceptibility of the bacterial isolates was assessed, a clear correlation between the nature of the antibiotics most frequently used as a first line of defense versus the resistance profile was observed. We conclude that the intensive use of antibiotics in an NICU setting with highly susceptible patients causes selection of multiresistant clones of CoNS which subsequently become endemic.

Anti-Bacterial Agents↗
PubMed1998

Antibody responses and opsonic activity in sera of preterm neonates with coagulase-negative staphylococcal septicemia and the effect of the administration of fresh frozen plasma.

Coagulase-negative staphylococcal septicemia is the most prominent nosocomial infection in neonatal intensive care units. Immaturity of host defenses in premature neonates is assumed to constitute an important risk factor. Opsonophagocytosis is considered to be the key host defense system against staphylococci with IgG antibodies as a major opsonin. For this reason we have studied serum IgG antibody titers and opsonic activity to coagulase-negative staphylococci in 20 infants with septicemia and 40 matched control subjects. In addition, we assessed the effect of administration of fresh frozen plasma (FFP) on IgG antibody titer and serum opsonic activity in 12 patients with septicemia. IgG antibodies, quantified by ELISA and opsonic activity, determined by flow cytometry, were expressed as a percentage of the value of pooled normal human reference serum. Both patients and control subjects showed low IgG titers (median, 21%; range, 1-192%) and a low opsonic activity (median, 33%; range, 8-484%) at birth. During the first 2 postnatal wk IgG titers decreased significantly in septicemia patients (from a median of 30 to 17%, p = 0.025), but not in control subjects, whereas opsonic activity remained unchanged. The titer of IgG antibodies increased significantly in septicemia patients after FFP administration (from a median of 17 to 41%, p = 0.002), whereas the effect on opsonic activity was unpredictable, showing a moderate increase in 10 out of 12 infants, and in 2 patients even a substantial decrease (>50%), despite adequate opsonic activity in the corresponding FFP batches. Immunoblotting of sepsis isolates with the corresponding patient sera demonstrated that septicemic infants may generate IgG antibodies against their blood isolate. Neonates who acquire coagulase-negative staphylococcal septicemia cannot be distinguished from control subjects on the basis of IgG antibodies and opsonic activity to staphylococci either at birth or during the first 2 postnatal wk. The administration of FFP to septicemia neonates has an unpredictable effect on opsonic activity and therefore does not seem to be a useful addition to antibiotic therapy.

Antibodies, Bacterial↗
PubMed1997

Release of tobramycin from tobramycin-containing bone cement in bone and serum of rabbits.

Tobramycin release from tobramycin-containing bone cement was studied in vivo in a rabbit model. After insertion of cement into the right femur, tobramycin concentration as a function of time for up to 28 days was measured in serum and bone of rabbits. Tobramycin release in the femoral cortex adjacent to the cement was found to exceed the minimal inhibitory concentration for Staphylococcus aureus Wood 46. Serum tobramycin concentrations were below the systemic toxicity threshold.

Journal Article↗