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Biomedical subjects

S Want

Publications and source records attributed to S Want.

9 recordsLinked to original sources

Development of a time-to-positivity assay as a tool in the antibiotic management of septic patients.

Optimal use of antibiotics is a key component of the management of sepsis. The purpose of this study was to develop a modification of the time-to-positivity (T(pos)) assay for use in the acute management of septic patients. Initial laboratory experiments, followed by ex-vivo validation and pilot studies, were performed with a small number of healthy human volunteers and 46 septic patients on a general intensive care unit, chosen on the basis of their antibiotic regimen. The study demonstrated that the T(pos) assay could be used as a surrogate for antimicrobial activity, and provided preliminary data to demonstrate how this approach might be used to monitor the efficacy of antibiotic therapy in septic patients. The T(pos) assay might offer a quick and convenient way to improve the efficacy of antibiotic therapy in septic patients, and further prospective large-scale studies are now warranted.

Anti-Bacterial Agents↗

Antibiotic prophylaxis in surgery of the intervertebral disc. A comparison between gentamicin and cefuroxime.

Antibiotics are often administrated prophylactically in spinal procedures to reduce the risk of infection of the disc space. It is still not known which antibiotics are able to penetrate the intervertebral disc effectively. In a prospective, randomised, double-blind clinical study, we examined the penetration of the intervertebral discs of two commonly used antibiotics, cefuroxime and gentamicin. The patients, randomised into two groups, received either 1.5 g of cefuroxime or 5 mg/kg of gentamicin prophylactically two hours before their intervertebral discs were removed. A specimen of blood, from which serum antibiotic levels were determined, was obtained at the time of discectomy. Therapeutic levels of antibiotic were detectable in the intervertebral discs of the ten patients who received gentamicin. Only two of the ten patients (20%) who received cefuroxime had a quantifiable level of antibiotic in their discs although therapeutic serum levels of cefuroxime were found in all ten patients. Our results show that cefuroxime does not diffuse into human intervertebral discs as readily as gentamicin. It is possible that the charge due to ionisable groups on the antibiotics can influence the penetration of the antibiotics. We therefore recommend the use of gentamicin in a single prophylactic dose for all spinal procedures in order to reduce the risk of discitis.

Adult↗

A new in-vitro model to investigate antibiotic penetration of the intervertebral disc.

We have studied the ability of a range of antibiotics to penetrate intervertebral disc tissue in vitro, using a mouse disc model. Equilibrium concentrations of antibiotics incorporated into the entire disc were determined by bioassay using a microbial growth-inhibition method. Uptake was significantly higher with positively-charged aminoglycosides compared with negatively-charged penicillins and cephalosporins. Uncharged ciprofloxacin showed an intermediate degree of uptake. Our results support the hypothesis that electrostatic interaction between charged antibiotics and negatively-charged glycosaminoglycans in the disc is an important factor in antibiotic penetration, and may explain their differential uptake.

Animals↗

A prospective, randomized comparison of ceftazidime and ciprofloxacin as initial empiric therapy in neutropenic patients with fever.

This study developed further clinical experience in using a single agent ("monotherapy") as empirical treatment for neutropenic patients with fever, and compared the safety and toxicity of two candidate agents, ceftazidime and ciprofloxacin. A prospective, randomized, single-center efficacy and safety comparison was conducted of intravenous ciprofloxacin, 200 mg every 12 hours, and ceftazidime, 2 g every eight hours, as initial empirical therapy in neutropenic patients with fever. Regimens were modified as necessary, guided by laboratory results and/or the clinical condition. Response was evaluated at 72 hours and at the end of the neutropenia. Toxicity was evaluated by regular clinical examination and laboratory investigations. A total of 43 patients with 51 febrile neutropenic episodes were enrolled into the study and randomly assigned to one of the two regimens. Five episodes were excluded from evaluation of efficacy because of protocol violations, leaving 46 evaluable episodes (21 ciprofloxacin, 25 ceftazidime). The two groups were well matched for risk factors for infection. There were no differences between the two groups in response rates either at 72 hours or at the end of neutropenia, although in the vast majority of patients some modification of the initial therapy was required. No patients died of uncontrolled bacterial infection. Superinfection with gram-positive cocci (often streptococci) was seen primarily in bone marrow transplant recipients who had been randomly assigned to receive ciprofloxacin. This study demonstrated that, in certain circumstances, a single antibiotic can be used successfully as initial empirical therapy in febrile neutropenic patients. In this study, ceftazidime and ciprofloxacin were generally of equal efficacy, but there appeared to be an increased incidence of streptococcal superinfection in bone marrow transplant recipients who received ciprofloxacin.

Adolescent↗

An open study of the safety and efficacy of enoxacin in complicated urinary tract infections.

Thirty-one patients with serious or complicated urinary tract infections were treated with oral enoxacin for between four and eight days. Twenty-five patients with microbiologically confirmed infections completed treatment with 400 mg enoxacin twice daily and at the end of treatment all urine cultures were negative. At short term follow-up, five to nine days after therapy, 21 of the 25 patients were still infection free. In total, reinfection or relapse occurred in 12 patients during the four to six weeks follow up period after termination of treatment. Significant side-effects (nausea and vomiting) occurred in only one patient.

Adult↗

Piperacillin in early neonatal infection.

Seventy infants with suspected bacterial infection in the first 48 hours of life were treated either with piperacillin and flucloxacillin or with penicillin and gentamicin. Infection was confirmed and successfully eradicated in 6 of the 35 infants receiving piperacillin and flucloxacillin. Four infants treated with penicillin and gentamicin had confirmed infection and one deteriorated initially but then recovered when treated with piperacillin. Serum piperacillin concentrations above 100 mg/l and cerebrospinal fluid piperacillin concentrations of 2.6-6 mg/l were noted for up to four hours and 7 hours respectively, even in the absence of inflamed meninges, after administration of piperacillin 100 mg/kg body weight intravenously. Median half life of piperacillin was 6.5 hours and was prolonged in renal impairment. Piperacillin is considered to be a safe and effective first line single agent treatment for early neonatal infection but because some Escherichia coli are resistant to it we recommend that a second agent be used in critically ill infants with neutropenia or meningitis.

Bacterial Infections↗

Prophylactic cefuroxime in total joint replacement.

Cefuroxime was given during operation to 95 patients undergoing 106 total joint replacements (hip 69: knee 37). Two regimes were used. Either 1 g was given intravenously with induction of anaesthesia and then two intramuscular injections of 1 g 6 and 12 h later, or 1.5 g was given intravenously with induction and two injections of 750 mg each intramuscularly 6 and 12 h later. The concentrations of cefuroxime in bone, capsule and blood were measured in 77 patients. The assays were carried out independently in two laboratories. In most instances concentrations in the bone were above the MICs for likely pathogens, even after allowing for any contaminating blood. Concentrations in synovial capsule were generally higher than in bone. After a follow-up period of 2 years, two patients developed deep infections. The overall infection rates are comparable with the best results reported in the literature using other prophylactic antibiotics or with ultra-clean air systems.

Adult↗