Quinolone-induced arthropathy: an update focusing on new mechanistic and clinical data

Quinolones possess favourable antibacterial and pharmacokinetic characteristics and are often used as anti-infective agents in adults. They are contraindicated in children and adolescents because they damage weight-bearing joints in juvenile animals. In addition, they possess a tendotoxic potential. Since ciprofloxacin has been used off-label for decades in children and adolescents, it is known today that no pronounced risks for arthropathies or tendinopathies exist in humans. Recently published clinical studies with gatifloxacin in children support this clinical experience. However, a low risk for joint disorders cannot be excluded and tendinopathies are a generally accepted rare adverse effect of quinolones at least in adults. Isolated case reports of arthralgia in children following quinolone therapy have been published and in studies with levofloxacin the incidence of musculoskeletal disorders was significantly greater in levofloxacin-treated patients than in control patients treated with comparator antibiotics. As a consequence, only life-threatening infections for which other antimicrobials cannot be used are possible indications for quinolones in children, for example the use of ciprofloxacin in cystic fibrosis patients with a bronchopulmonary exacerbation, chronic suppurative otitis media caused by Pseudomonas sp., complicated urinary tract infections and enteritis caused by invasive multidrug-resistant pathogens (e.g. Salmonella, Shigella).     

Booster vaccination of adults with reduced-antigen-content diphtheria,Tetanus and pertussis vaccine: Immunogenicity 5 years post-vaccination

At 60 months post-vaccination, adults (mean age 45.6 years) randomised to receive combined reduced-antigen-content diphtheria–tetanus and acellular pertussis vaccine (dTpa) versus tetanus–diphtheria (Td) + monovalent acellular pertussis (pa) were seroprotected against diphtheria (≥0.016 IU/mL Vero cell assay) and tetanus (≥0.1 IU/mL ELISA assay) in 94.4% and 96.2%, respectively (dTpa), compared with 93.7% and 90.6% (Td + pa). Anti-FHA, anti-PT and anti-PRN antibodies (≥5 EL.U/mL) were maintained in 100%, 89.5% and 95.0% of dTpa versus 100%, 85.5% and 90.6% of pa vaccine recipients. At 5 years post boosting, antibody levels to diphtheria and tetanus are similar amongst adults receiving a dTpa or dT, and pertussis antibodies remain above pre-booster levels in at least 85%.     

Blood stream infections of abdominal origin in the intensive care unit: characteristics and determinants of death

BACKGROUND: Blood stream infections (BSI) of abdominal origin are associated with a high mortality rate. We hypothesized that both patient and microbiological factors determine death in critically ill patients who develop such infections. METHODS: Ninety-six consecutive patients who developed BSI of abdominal origin in an 11-year period (1992-2002) in the intensive care unit (ICU) of the Ghent University Hospital were studied. Patient data were retrieved from a prospective registry of BSI. Demographics, disease severity, source of the BSI, incidence of organ failure, and outcome were recorded. Microbiological data were retrieved from the patient file and the hospital laboratory. RESULTS: Secondary peritonitis and intra-abdominal abscesses were the source of the BSI in the majority of patients. The majority of the organisms involved were gram-negative, with Escherichia coli isolated most frequently. Twenty-one patients (22%) had polymicrobial BSI, and in 39 patients, at least one of the micro-organisms was antibiotic resistant (41%). The mortality rate in the whole patient group was 62.5% (60/96), which was significantly higher than the Acute Physiology and Chronic Health Evaluation (APACHE) II-based expected mortality rate (p < 0.001). Patients who died were older, had a tendency to have a higher APACHE II score on admission, and were more likely to suffer from acute renal failure and cardiovascular failure during their ICU stay. Logistic regression analysis revealed that the following factors were independently associated with death: Age (odds ratio [OR] 1.09; 95% confidence interval [CI] 1.04, 1.14; p < 0.001) (per year increase) and the occurrence of acute renal failure (OR 4.18; 95% CI 1.22, 14.31; p = 0.023). CONCLUSIONS: The mortality rate of ICU patients who develop BSI of intra-abdominal origin is high. Gram-negative micro-organisms were isolated most frequently, and 41% of all organisms were antibiotic-resistant. Two patient-related factors (greater age and the development of acute renal failure) were associated independently with a higher mortality rate.     

Prospective study of sequential reduction in immunosuppression, interferon alpha-2B, and chemotherapy for posttransplantation lymphoproliferative disorder

BACKGROUND: Several interventions can cure posttransplant lymphoproliferative disease (PTLD); a sequential approach is usual, starting with reduction in immunosuppressives (RI). The efficacy of RI remains poorly defined, particularly in adults. We assessed an algorithm starting with a defined course of RI in all patients, escalating to interferon (IFN) alpha2b, and finally to chemotherapy, in a prospective multicenter phase II study of adult solid organ transplant recipients. The design predated rituximab. METHODS: Reduction in immunosuppressives: cyclosporine or tacrolimus reduction by 50% for 2 weeks; a further 50% reduction for 1 week if not in complete remission (CR). Intravenous acyclovir was given for the duration of all RI. Patients with less than CR, or any rejection, resumed immunosuppressives and proceeded to IFN 3 MIU/m(2)/day for up to 3 months; if less than CR, ProMACE-CytaBOM chemotherapy. RESULTS: Twenty patients were registered over 60 months; 16 patients with biopsy-proven PTLD were eligible (13 heart, 3 kidney recipients). Median age was 47 (24-75) years. Reduction in immunosuppressives resulted in only 1 of 16 partial responses (12.5%), no CR. Progressive disease occurred in 8 of 16 (50%) and 6 of 16 (38%) experienced rejection. Only 1 of 13 (7%) patients achieved durable CR with IFN. Seven eligible patients received ProMACE-CytaBOM chemotherapy, five of seven (67%) achieving CR, four of five durable beyond 2 years. CONCLUSIONS: Reduction in immunosuppressives produced no CR, progressive disease and rejection were frequent; response to IFN was rare. A strong case can be made for adding rituximab to RI as initial therapy. Chemotherapy resulted in 57% durable CR, data that are relevant for the up to two thirds of PTLD patients who are refractory to rituximab.     

Flavobacterium meningosepticum, a pathogen in birds.

Five bacterial isolates were recovered from various diseased birds (chickens, a pigeon, and a zebra finch) and were identified as Flavobacterium meningosepticum. Four of them were isolated in pure or nearly pure culture of samples from internal organs, and one strain was isolated in mixed culture of a tarsal joint fluid sample. Except for the last case, there was no evidence of other disease agents. By using phenotypic, chemotaxonomic, and genomic methods, the strains were taxonomically characterized and could not be differentiated from the human clinical reference strains of the species. Two avian strains were different in their phenotypic behaviors and constituted another genotypic subgroup. In general, all F. meningosepticum strains constituted a single species which was easily differentiated from biochemically similar species and phylogenetically closely related taxa.     

Assessment of renal function in recently admitted critically ill patients with normal serum creatinine.

BACKGROUND: Detection of renal dysfunction is important in critically ill patients, and in daily practice, serum creatinine is used most often. Other tools allowing the evaluation of renal function are the Cockcroft-Gault and MDRD (Modification of Diet in Renal Disease) equations. These parameters may, however, not be optimal for critically ill patients. The present study evaluated the value of a single serum creatinine measurement, within normal limits, and three commonly used prediction equations for assessment of glomerular function (Cockcroft-Gault, MDRD and the simplified MDRD formula), compared with creatinine clearance (Ccr) measured on a 1 h urine collection in an intensive care unit (ICU) population. METHODS: This was a prospective observational study. A total of 28 adult patients with a serum creatinine <1.5 mg/dl, within the first week of ICU admission, were included in the study. Renal function was assessed with serum creatinine, timed 1 h urinary Ccr, and the Cockcroft-Gault, MDRD and simplified MDRD equations. RESULTS: Serum creatinine was in the normal range in all patients. Despite this, measured urinary Ccr was <80 ml/min/1.73 m2 in 13 patients (46.4%), and <60 ml/min/1.73 m2 in seven patients (25%). Urinary creatinine levels were low, especially in patients with low Ccr, suggesting a depressed production of creatinine caused by pronounced muscle loss. Regression analysis and Bland-Altman plots revealed that neither the Cockcroft-Gault formula nor the MDRD equations were specific enough for assessment of renal function. CONCLUSIONS: In recently admitted critically ill patients with normal serum creatinine, serum creatinine had a low sensitivity for detection of renal dysfunction. Furthermore, the Cockcroft-Gault and MDRD equations were not adequate in assessing renal function.     

Induction of autologous graft-versus-host disease: results of a randomized prospective clinical trial in patients with poor risk lymphoma.

The results of blood or marrow transplantation in patients with chemorefractory aggressive lymphoma, that is, those not responding to conventional-dose chemotherapy at the time of transplant, have been poor. The relapse rate has been high after autologous bone marrow transplant, whereas allogeneic transplantation has been associated with excessive transplant-related toxicity. Administration of cyclosporine after autologous transplantation can induce an autoreactive syndrome that resembles graft-versus-host disease (GVHD). This syndrome, named autologous graft-versus-host disease, has clear antitumor activity in animal models that can be enhanced by the addition of cytokines such as gamma-interferon and interleukin-2. A randomized, prospective study was conducted to evaluate the antitumor effect of autologous graft-versus-host disease induced with cyclosporine, and augmented by the administration of gamma-interferon and interleukin-2 in patients with chemorefractory Hodgkin and aggressive non-Hodgkin lymphomas. Fifty-one patients were randomized, 24 to the autologous GVHD induction arm, and 27 to the noninduction arm after autologous transplant using mobilized peripheral blood stem cell (PBSC) grafts. There were no differences in treatment-related mortality, overall and event-free survival (OS, EFS) between both groups; however, in the induction arm, GVHD developed only in 4 patients. The administration of oral cyclosporine followed by interleukin-2 and gamma-interferon is generally not well tolerated, and does not appear to be an effective method to induce autologous GVHD in patients receiving autologous PBSC grafts.     

Coccidiostatic effects of tannin-rich diets in rabbit production

Parasitology Research - The potential anti-eimerial effect of tannin containing resources such as sainfoin and carob in rabbits was tested on does at pre-weaning and to growing rabbits in their...