Number Of Bacterial Infections Research Articles

A Randomized, Doubleblind, Placebo-Controlled, Study of Single-Dose Rituximab as Induction in Renal Transplantation

We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event. We enrolled 140 patients (44 living donor and 96 deceased donor), and of those, 68 rituximab and 68 placebo patients fulfilled the study. In all the patients receiving rituximab, there was a complete depletion of CD19/CD20 cells, whereas there was no change in the number of CD19/CD20 cells in the placebo group. There were 10 treatment failures in the rituximab group versus 14 in the placebo group (P=0.348). There were eight rejection episodes in the rituximab group versus 12 in the placebo group (P=0.317) Creatinine clearance was 66+/-22 mL/min in the study group and 67+/-23 mL/min in the placebo group. There was no difference in the number of bacterial infections, cytomegalovirus infections, and BK virus infections or fungal infections. We performed a placebo-controlled study of rituximab induction in renal transplantation. There was a tendency toward fewer and milder rejections during the first 6 months in the rituximab group. Although induction with one dose of rituximab induced a complete depletion B cells, there was no increase in the incidence of infectious complications or leukopenia and it seems safe, therefore, to conduct further studies on the use of rituximab in transplantation.

Vancomycin-Resistant Enterococci, Point Barrow, Alaska, USA

To the Editor: An increasing number of bacterial infections are now difficult or impossible to treat (1) because of the misuse of antimicrobial drugs and the epidemic spread of bacterial resistance to these drugs (2). The most alarming reports are of methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase producers, and vancomycin-resistant enterococci (VRE). Although knowledge about dissemination mechanisms is poor, the spread of resistance clearly is not restricted to hospitals but occurs also in the community and in the natural environment (3,4). Since the 1990s, the epidemiology in the United States has shifted so that most VRE are Enterococcus faecium. Recent studies indicate clonal spread of the E. faecium CC17 lineage in clinical isolates, exhibiting high-level ampicillin and fluoroquinolone resistance and harboring an enterococcal surface protein–coding esp gene (5,6). During a polar research expedition to the Beringia region in 2005, we collected fecal samples from birds at sites with no or low human population. The aim was to investigate the current status of resistance dissemination into remote areas of the world. The study site in Alaska was located on the tundra halfway between the city of Barrow and Point Barrow, the northernmost point of the United States (71°23′20″N, 156°28′45″W). Fecal samples from glauocus gulls (Larus hyperboreus) were enriched (18 h at 37°C) in brain–heart infusion broth (Becton Dickinson, Franklin Lakes, NJ, USA) supplemented with aztreonam and vancomycin (10 mg/L and 4 mg/L, respectively; ICN Biomedicals Inc., Aurora, OH, USA), followed by spreading on chromID VRE plates (bioMerieux, Marcy l’Etoile, France) and incubated for 48 h at 37°C. Typical colonies were isolated and species identified by biochemical testing, including the Phoenix Automated Microbiology System (Becton Dickinson). MIC was determined for vancomycin, teicoplanin, ampicillin, and ciprofloxacin by using Etest strips (AB Biodisk, Solna, Sweden), and the presence of vanA, vanB, and esp genes was established by PCR with previously described primers (7,8) (esp primers esp11 and esp12). Cultures showed 2 isolates of E. faecium; MICs for vancomycin and teicoplanin were >256 and 96 µg/mL, respectively, for both isolates. Genotyping determined that they harbored vanA. Isolates exhibited high-level ampicillin and ciprofloxacin resistance; MICs were >256 and >32 µg mL, respectively for both isolates. They also harbored the esp gene. Isolates came from 2 of 33 sampled glaucous gulls, a species confined to the Arctic regions, that have limited southbound migration during the nonbreeding season. Clinical isolates of VRE were first found in the late 1980s. In the United States, vancomycin was widely used in human medicine, and outbreaks occurred in hospitals rather than in the community; the opposite was, and is, true in Europe. Because of massive use of glycopeptide antimicrobial drugs, i.e., avoparcin, as growth promoters in domestic animal production until the mid-1990s, VRE can be found in hospitals and the community (9). Our findings show that bacteria resistant to antimicrobial drugs, or resistance genes, already have spread to one of the most remote areas of North America, Point Barrow, Alaska. This spread suggests that few (if any) places on earth may be protected against the spread of such resistance, and the dispersal mechanisms are far more efficient than previously thought. Our data also place the isolates as part of the clinically spread clonal E. faecium CC17 lineage, characterized by high-level ampicillin and quinolone resistance and harboring the esp gene, thus strongly supporting a human origin. Possible dispersal mechanisms to remote areas include stepwise horizontal transfer between migratory and nonmigratory bird species and anthropogenic transport. The increasing evolution and spread of antimicrobial drug–resistant bacteria and resistance genes seriously threaten public health and could escalate to catastrophic proportions (1). Bacteria and drug resistance are easily transferred between humans and animals and consequently between the environment and clinical settings. Much remains to be learned about the effect of human-associated changes of natural ecosystems on the total effect of resistance. Therefore, our finding of VRE at Point Barrow is important to recognize. Decisive action is needed to establish efficient monitoring programs that include not only surveillance and control of clinical bacterial resistance but also environmental levels of resistance.

Association of MBL2 genotypes wtih infections and outcome after allogeneic stem cell transplantation

7100 Background: Low MBL2 concentration and MBL2 genotype variants have been associated with an increased risk of infection. Our objective was to correlate MBL2 genotypes with specific infections and outcome of HSCT. Methods: 125 non- consecutive, non-selected HSCT were examined. Patients were classified as high or low risk group based on status of underlying disease. Antifungal prophylaxis consisted of fluconazole 400 mg daily. Patients on steroids received mould prophylaxis. There was no routine antibacterial prophylaxis. Microbiologically confirmed infections were recorded. Genotype was determined by PR-Melting Curve Analysis on blood or buccal swab specimens. MBL genotype was classified as wild-type: A/A (MBL-sufficient, MBL-S) or variant-type: A/O, O/O (MBL deficient, MBL- D). Patients were followed for up to 2 years. Analyses of categorical variables were performed using the Fisher exact test and the Log-Rank test for time to event. Results: Seventy-one (58.2%) patients were homozygous for wild-type MBL2 (AA), 43 (35.3%) were heterozygous (A/0) and 8 (6.5%) were homozygous for variant genotypes (OO). MBL-D group had higher incidence of fungal infections (20% vs 7%, p=0.05), and in particular Aspergillosis (12% vs 3%, p=0.05). MBL-D was associated with a trend for higher rates of bacterial infections (63% vs 46%, p=0.10) and total number of bacterial infections (p=0.10). Rates of respiratory and enteric viral infections or CMV were similar in MBL-D and MBL-S groups (41% vs 38%, p=0.9 and 58% vs. 54% p=1.0 respectively). Patients with MBL-D genotype were at a disadvantage in relapse-free (RFS) and overall survival (OS), (p<0.01 and p=.08). This disadvantage was also observed when stratified by disease risk groups. The estimated 2-year relapse-free survival rate was 30% compared to 53% for MBL-D vs. MBL-S patients (p<0.01). Conclusions: 1) Patients with variant MBL genotype (MBL-D) had a trend for increased incidence and number of bacterial infections. 2) MBL-D genotype and graft versus host disease were risk factors for aspergillosis. 3) MBL-D genotype was associated with worse overall survival and relapse free survival post HSCT. These data suggest that MBL-D patients have impaired immune function compared with MBL-S patients and is consistent with animal data. [Table: see text]

Blood Group Antigen Recognition by Escherichia coli Heat-labile Enterotoxin

In a number of bacterial infections, such as Helicobacter pylori, Campylobacter jejuni and Vibrio cholerae infections, a correlation between the severity of disease and blood group phenotype of infected individuals has been observed. In the present investigation, we have studied the molecular basis of this effect for enterotoxigenic Escherichia coli (ETEC) infections. ETEC are non-invasive bacteria, which act through second messenger pathways to cause diarrhea. It has been suggested that the major virulence factor of ETEC from human isolates, i.e. the human heat-labile enterotoxin (hLT), recognizes certain blood group epitopes, although the molecular basis of blood group antigen recognition is unknown. The 2.5 Å crystal structure of the receptor-binding B-subunit of hLT in complex with the blood group A antigen analog GalNAcα3(Fucα2)Galβ4(Fucα3)Glcβ provides evidence of a previously unknown binding site in the native toxin. The structure reveals the molecular interactions underlying blood group antigen recognition and suggests how this protein can discriminate between different blood group epitopes. These results support the previously debated role of hLT in the blood group dependence of ETEC infections. Similar observations regarding the closely related cholera toxin in V. cholera infections are also discussed.

Voriconazole in Primary Prophylaxis Reduces the Incidence of IFI in High Risk Hematologic Patients.

OBJETIVE: To analyse the eficacy and safety of voriconazole as primary prophylaxis in hematologic patients with high risk of invasive fungal infections (IFI) due to severe neutropenia after induction/intensification chemotherapy for acute myeloid leukemia (AML) and allogeneic hematopoietic cell transplantation (allo-HCT).PATIENTS AND METHODS: between June-04 and May-05 we prospectively included 31 episodes of severe neutropenia (<0,5x109/l, >10 days) after chemotherapy for AML and 24 patients submitted to an allo-HCT in a primary prophylaxis treatment with voriconazole (200 mg po/12 h) from the starting of chemotherapy until the neutrophils recovery (>0,5x109/l) in AML and from the starting of the conditioning regimen until the withdrawal of immunossupression in allo-HCT (by three months after transplantation) and we compared both groups with historic controls (63 episodes of neutropenia after AML and 31 allo-HCT) treated between January-03 and May-04 with fluconazole as primary prophylaxis (400 mg po/24 h) in the same way. Drugs were adjusted to weight in children. In case of severe mucositis voriconazole or fluconazole were temporarily used intravenously. EORTC/MSG criteria for IFI definitions were used and galactomanane antigen determinations were done twice a week. In case of neutropenic fever, empiric antifungal treatment was started in the fith day with lyposomal amfotericin B the primary prophylaxis was stopped.RESULTS: AML GROUP: We didn't find statistical differences among groups of VORI (n=31) and FLUCO (n=63) when we analyse age (VORI mean 49y, 18–64;FLUCO mean53y,21–72), sex, FAB classification, disease status, number of broad spectrum antibiotics, bacterial infections, days of neutropenia (19 vs 18) and days of fever (5.8 vs 7.2). The number of detected IFI was superior in the fluconazole group in spite of no statistical differences (VORI 3 vs FLUCO 11; 9,6% vs 17,4%, p=NS) with a sum of proven+probable 2 vs 5 (6,4% vs 8%, p=NS). Interestingly, the number of fatal IFI was statistical superior in the fluconazole group (VORI 0 vs FLUCO 4, p<0,05) and the need for empiric antifungal treatment was superior in the fluconazole group (VORI 19,3% vs FLUCO 50,8%, p=0,004). None patient had to interrupt voriconazole due to toxicity.ALLO-HCT GROUP: we didn't find statistical differences among groups of VORI (n=24) and FLUCO (n=31) when we analyse age (VORI mean 37y, 2–64 and FLUCO mean 30y, 5–56), sex, diagnosis and status at transplantation. In spite of differences in the conditioning regimen with more reduced-intensity conditioning regimen in the voriconazole group, both groups were similar when we analyse incidence of aGVHD II–IV grades, steroids use, VOD, number of bacterial infections, CMV infections and cGVHD. The days of fever were superior in the fluconazole group (VORI 4 vs FLUCO 7, p=0,04) and so the need for empiric antifungal treatment (VORI 6 vs FLUCO 16, p=0,042). The number of IFI was superior in the fluconazole group (VORI 2 vs FLUCO 10, p=0,04) and the number of fatal events due to IFI was superior in the fluconazole group (VORI 1 vs FLUCO 5, p<0,05). Voriconazole was temporarily stopped in two patients with hepatic aGVHD and one patient with VOD. Three patients developped hepatic colestasis by day +75 wich was reversible after discontinuating voriconazole one week.CONCLUSSIONS: voriconazole as primary prophylaxis of IFI is a safety and well tolerated efective drug wich reduces the need for empiric antifungal treatment and the fatal events due to IFI in AML and allo-HCT.

Influence of Age in Renal Transplant Infections: Cases and Controls Study

Kidney transplantation in elderly patients is a good therapeutic option, but the incidence of infections compared to younger patients must be studied. Case and control study was performed with 40 cases (patients older than 65) and 40 controls (younger than 65) receiving a kidney transplant between January 2000 and August 2002. In 32 cases (80%) and in 14 controls (32%), some type of infection appeared during the follow-up (odds ratio [OR] 5; 95% CI 1.6-20). The percentage of patients with bacterial infections was higher in the cases (70% vs. 28%; OR 5.7; 95% CI 1.9-20), especially for urinary infections. No differences for viral and fungal infections were observed in the two groups. Mortality rate was 13% in the cases (5% due to infections), whereas there was no controls' mortality. Although the number of bacterial infections was higher, kidney transplantation in elderly patients is a secure procedure.

Complications of systemic corticosteroid therapy for problematic hemangioma.

Systemic corticosteroid therapy has been used to treat hemangiomas for 30 years; yet, there are no studies of possible complications. We reviewed the database of the Vascular Anomalies Center at the Boston Children's Hospital and gathered information on short- and long-term side effects in children who were given systemic corticosteroids for problematic hemangiomas. In addition, a questionnaire regarding early and late consequences was sent to the families of children who were treated with corticosteroids from 1983 to 1997. Of 300 patients with hemangiomas, 80 children were identified as having received a full course of systemic corticosteroids for problematic tumors. Complete data were collected on 62 of these children. The response rate to the questionnaire was 78 percent (n = 62 of 80). The initial dose of corticosteroid varied from 2 to 3 mg/kg/ day. Duration of therapy ranged from 2 to 21 months (mean, 7.9 months; median, 6.5 months). The follow-up interval from the cessation of therapy ranged from 6 months to 15 years (mean, 4 years; median, 3 years). Short-term complications included cushingoid facies (n = 44; 71 percent), personality changes (n = 18; 29 percent), gastric irritation (n = 13; 21 percent), fungal (oral or perineal) infection (n = 4; 6 percent), and diminished gain of height (n = 22; 35 percent) and weight (n = 26; 42 percent). A total of 91 percent of children who had diminished gain of height (n = 20) returned to their pretreatment growth curve for height by 24 months of age. One child, who was treated at another institution with a dose of 20 mg/kg/day for 6.5 months that was slowly tapered over 18 months, was petite 6 years after ending therapy. Another child treated with an initial dose of 2 mg/kg/day for 5 months was smaller than predicted at the age of 6 years, but she was born prematurely and was on ventilatory support for respiratory distress. Three children treated with the standard dose and duration were at a low percentile for weight 4, 5, and 10 years after the cessation of therapy. Statistical analysis showed a correlation between diminished gain of height with duration of therapy and age at initiation of treatment. One child had corticosteroid myopathy that resolved with cessation of therapy. We found no evidence for immunologic suppression, i.e., there was no increase in the number of bacterial infections during corticosteroid administration. In conclusion, systemic corticosteroids can be safely given to treat endangering hemangiomas in infants at doses of 2 to 3 mg/kg/day, which are slowly tapered and stopped before the age of 1 year. Short-term side effects were minor and transient, and no serious long-term complications occurred.

Example of Prepublication Data Release: Immunoglobulin for Concomitant Infections

INTRAVENOUS injection of a broad-spectrum immunoglobulin significantly reduces the number of bacterial infections in some children who are infected with the human immunodeficiency virus (HIV). It also significantly increases the time patients are free of infection and reduces the number of hospitalizations. These are the results of a double-blind, placebo-controlled study by the National Institute of Child Health and Human Development, Bethesda, Md. However, despite these findings, there was no effect on mortality. Thirty-one patients died in each of the two groups studied. The treatment is not a cure for pediatric acquired immunodeficiency syndrome (AIDS). The institute's parent, the National Institutes of Health, released the results prior to publication in a scientific journal, says the acting director, William Raub, PhD, in accordance with a proposed new system. (Please see related article on page 949.) "We believe these results have the prospect for an immediate and positive effect on the treatment

Serum immunoglobulin G subclasses in children infected with human immunodeficiency virus type 1

We studied serum concentrations of IgG subclasses in 47 human immunodeficiency virus 1-infected (17 asymptomatic and 30 symptomatic) children. Thirty-nine of 47 (83%) had an abnormality of at least 1 subclass. Sixteen had only elevated IgG1, 6 had only elevated IgG3 and 12 had elevated IgG1 and IgG3 concentrations. IgG2, IgG4 and combined IgG2-IgG4 deficiency was found in 3, 4 and 4 patients, respectively. IgG2 concentrations did not differ between patients with (n = 23) or without (n = 24) bacterial infections. Additionally the number of bacterial infections was similar between the patients with normal or low IgG2 and/or low IgG4. These data indicate that IgG subclass abnormalities are found in most children with human immunodeficiency virus 1 infection, but quantitative deficiencies of specific subclasses do not appear to explain the high frequency of bacterial infections occurring in these patients.

Effects of magainins and cecropins on the sporogonic development of malaria parasites in mosquitoes

Magainins and cecropins are families of peptides with broad antimicrobial and antiparasitic activities derived respectively from the skin of frogs or from giant silk moths. In insects, cecropins function as part of an inducible immune system against a number of bacterial infections. When injected into anopheline mosquitoes previously infected with a variety of Plasmodium species, both magainins and cecropins disrupt sporogonic development by aborting the normal development of oocysts; sporozoites are not formed and the vector cannot transmit the parasite to another host. It may be possible to induce effective transmission-blocking immunity in the mosquito vector by the introduction and expression of genes coding for magainins, cecropins, or similarly acting parasiticidal peptides into the mosquito genome.

An Evaluation of Oleandomycin as a Control of American Foulbrood Disease of Honey Bees

Oleandomycin is a relatively new antibiotic produced by Sterptomyces antibioticus, a fungus belonging to the Actinomycetes. These fungi are widely found in soils and composts, in air and on dust particles and in close association with plants. Oleandomycin was first described in 1954 under the designation P.A. 105. Chemically it is a basic compound composed of the sugars L-oleandrose and desosamine, glycosidically attached to a complex lactone nucleus, termed oleandolide. The approximate empirical formula is C37H31NO12. This chemical is used medicinally in the treatment of a number of bacterial infections of man. It has also been shown to be effective against viruses, rickettsia and certain protozoa. Combinations of oleandomycin with other antibiotics, primarily with terramycin, are popular, and there are indications that certain combinations achieve both synergistic action and a suppression of the development of resistant bacteria (Colville et al. 1959). The colonies of bees used in this experiment were obtained by the local bee inspector from several beekeepers. They were in both 8 and 10 frame hives with one to three honey supers. All were infected with American foulbrood. Four levels of oleandomycin were tested. They were 0.125, 0.25, 0.5 and 1 gram of oleandomycin per treatment. Each treatment was replicated three or more times. The oleandomycin used was a 25 per cent concentrate obtained from Chas. Pfizer & Company. Each test level of oleandomycin was thoroughly mixed in one-fourth cup of powdered sugar by sifting 4 times through a kitchen flour sifter. A simple method of application of the antibiotic was used (Fig. 1). The hives were opened, exposing the brood nest, and the mixture of oleandomycin and powdered sugar was dusted with a flour sifter evenly over the top bars of the brood frames. Applications were repeated in this manner at one to two week intervals until the disease disappeared. No manipulation of the hive to induce brood rearing in all brood frames or super frames was attempted. No honey, which could harbor disease spores, was removed from the hive. This simplified method of treatment was selected because if successful it would be practical in comnmercial beekeeping. The method required the minimum of time for the treatment, was inexpensive, and disrupted the colony as little as possible, thereby preventing robbing and a chance of spreading disease through the apiary. Observations were made of each hive at time of treatment. Records were kept as to the amount of disease present, the population of the hive, conditions of the brood and queen, and the amount of honey in the hive.

Models for a Bacterial Growth Process with Removals

SUMMARY The paper considers the extinction of a bacterial colony subject to phage infection. A description of the biological process leads to the construction of a simplified model from which it is possible to derive the probability generating function (p.g.f.) for surviving bacteria in terms of repeated contour integrals. The distributions of phage offspring released by a single bacterium, and of bacterial infections due to these phages, are discussed. For bacterial birth and birth-death processes, it is possible to express the p.g.f. for surviving bacteria explicitly; this is done by first obtaining the p.g.f. conditional on numbers of bacterial infections, and then summing over all such possible infections.

Derivatives of bis (4‐aminophenyl)‐sulfone I. Vitamin C Derivatives of Bis (4‐aminophenyl)‐sulfone and Related Sulfa Drugs

AbstractIn order to improve the chemotherapeutic value of bis (4‐aminophenyl)‐sulfone, an agent active against tuberculosis, leprosy, and a number of bacterial infections but too toxic for clinical use, it was condensed with vitamin C (1‐ascorbic acid) in methanol solution to form a crystalline product.This new derivative has a LD 50 of 987.7 ± 94.8 mg per kilo (mice, oral). Compared with the LD 50 of bis (4‐aminophenyl)‐sulfone, which is 12.6 mg/kilo (mice, oral), the vitamin C derivative is only one eightieth as toxic. In a concentration of 0.2 mg per 10 cm3 culture, it inhibited completely the growth of T. B. from 96 to 168 hours; in a concentration of 0.02 mg per 10 cm3 culture, it was found to be still bacteriostatic.The vitamin C derivatives of sulfa drugs were also prepared and studied.The antitubercular activity of the vitamin C derivatives of sulfathiazole, sulfadiazine and sulfamerazine was found to be of the same magnitude as salicylacetone, which inhibited completely the growth of T.B. in a concentration of 2 mg per 10 cm3 culture.

Utilization of Wheat Bran for Streptomycin Production by S. griseus

THE study of the nutritive requirements of Streptomyces griseus has assumed great importance on account of the remarkable activity of streptomycin against a number of bacterial infections. A number of media in which successful antibiotic production takes place have been recorded in the literature1–5. During the course of investigations on streptomycin production, aqueous extracts of wheat bran were found to give encouraging results; the methods of preparation and composition of the extract are described elsewhere6. By the procedure employed, about 4,000 ml. of the extract with about 3 per cent total solid content can be prepared from 1,000 gm. of bran.