Brain substrates of unhealthy versus healthy food choices: influence of homeostatic status and body mass index.

BACKGROUND/OBJECTIVES: Unhealthy dietary choices are a major contributor to harmful weight gain and obesity. This study interrogated the brain substrates of unhealthy versus healthy food choices in vivo, and evaluated the influence of hunger state and body mass index (BMI) on brain activation and connectivity. SUBJECTS/METHODS: Thirty adults (BMI: 18-38 kg m-2) performed a food-choice task involving preference-based selection between beverage pairs consisting of high-calorie (unhealthy) or low-calorie (healthy) options, concurrent with functional magnetic resonance imaging (fMRI). Selected food stimuli were delivered to participants using an MRI-compatible gustometer. fMRI scans were performed both after 10-h fasting and when sated. Brain activation and hypothalamic functional connectivity were assessed when selecting between unhealthy-healthy beverage pairings, relative to unhealthy-unhealthy and healthy-healthy options. Results were considered significant at cluster-based family-wise error corrected P<0.05. RESULTS: Selecting between unhealthy and healthy foods elicited significant activation in the hypothalamus, the medial and dorsolateral prefrontal cortices, the anterior insula and the posterior cingulate. Hunger was associated with higher activation within the ventromedial and dorsolateral prefrontal cortices, as well as lower connectivity between the hypothalamus and both the ventromedial prefrontal cortex and dorsal striatum. Critically, people with higher BMI showed lower activation of the hypothalamus-regardless of hunger state-and higher activation of the ventromedial prefrontal cortex when hungry. CONCLUSIONS: People who are overweight and obese have weaker activation of brain regions involved in energy regulation and greater activation of reward valuation regions while making choices between unhealthy and healthy foods. These results provide evidence for a shift towards hedonic-based, and away from energy-based, food selection in obesity.

Patient-reported outcomes following surgery for adolescent idiopathic scoliosis performed in adolescence versus adulthood.

INTRODUCTION: The Scoliosis Research Society 22r (SRS-22r) questionnaire is a proven tool in assessing healthcare-related quality of life (HRQoL) in idiopathic scoliosis and is the adopted patient-reported outcome measure for the deformity pathway recorded into the British Spinal Registry (BSR). Surgery for adolescent idiopathic scoliosis (AIS) is performed frequently in teenagers; however, patients also present with curves in the surgical range into adulthood. This work aimed to assess HRQoL differences between patients following surgery for AIS performed in adolescence and adulthood using SRS-22r data collected from the BSR. METHODS: An anonymised BSR search of pre- and postoperative SRS-22r scores for patients with diagnoses of AIS and adult idiopathic scoliosis was conducted. Data from all subdomains were compared preoperatively and at the two-year postoperative timepoint. RESULTS: Preoperative SRS-22r scores were analysed for 1,912 patients with AIS and 65 with adult idiopathic scoliosis. Patients with adult idiopathic scoliosis had significantly lower preoperative SRS-22r scores in all subdomains (p<0.05). By two years postoperatively, both groups of patients had improved SRS-22r scores significantly compared with baseline in all subdomains (p<0.001). A cross-group analysis revealed patients with AIS had significantly better function scores years postoperatively than their adult counterparts (p=0.005). CONCLUSIONS: This work confirms there are benefits following surgery for AIS in improving HRQoL, but has also provided HRQoL data in adult patients, who again show similar improvements following surgery from baseline. This is of value when counselling patients regarding anticipated benefits of surgery performed in childhood and adulthood.

A slip above a slip: retrolisthesis of the motion segment above a spondylolytic spondylolisthesis.

OBJECTIVE: The purpose of this study is to assess the degenerative changes in the motion segments above a L5S1 spondylolytic spondylolisthesis and to view these in light of the retrolisthesis in the segment immediately above the slip. A spondylolytic spondylolisthesis causes an abnormal motion and predisposes to degenerative changes at the L5S1 disc. Degenerative changes in the adjacent segments would influence the symptomatology and natural history of the disease and the treatment options. The extent of degenerative changes in the levels immediately above a L5S1 spondylolytic spondylolisthesis is not well documented in the literature. We have noted retrolisthesis at this level, but this has not been previously reported or assessed. MATERIALS AND METHODS: Thirty-eight patients with a symptomatic L5S1 spondylolytic spondylolisthesis with a mean age of 52.8 years (95% CI 47.2-58.4); 55.3% (n = 21) females and 44.7% (n = 17) males. We assessed the lumbar lordosis, slip angle, sacral slope, grade of the slip, facet angles at L34 and L45 on both sides, facet degenerative score (cartilage and sclerosis values), disc degenerative score (Pfirrmann) at L34, L45 and L5S1 and the presence of retrolisthesis at L45. RESULTS: We noted that 29% (11) had a retrolisthesis at L45. The degenerative scores reduced significantly from L5S1 through L45 and L34. Slip angle and L45 disc degenerative score were the only factors that occurred consistently in patients with a retrolisthesis. CONCLUSIONS: There is a cascade of degenerative changes that involve both the disc and the facet joints at the levels above a spondylolytic spondylolisthesis. The degenerative changes at the L45 disc and a higher slip angle are consistent findings in patients with a retrolisthesis at the level above the slip.

Shorter and sweeter: the 16-item version of the SRS questionnaire shows better structural validity than the 20-item version in young patients with spinal deformity.

PURPOSE: In patients with adult spinal deformity, it was previously shown that 16 of the non-management items of the SRS-instrument showed a better fit to the theoretical four-factor model (pain, function, self-image, mental health) than did all 20 items. Whether the same phenomenon is observed in data from younger (< 20y) patients, for whom the questionnaire was originally designed, is not currently known. METHODS: Confirmatory factor analysis was used to evaluate the factor structure of the 20 non-management items of the SRS-instrument completed by 3618 young patients with spinal deformity (75.5% female; mean age, 15.0 ± 2.0 years) and of its equivalence across language versions (2713 English-speaking, 270 Spanish, 264 German, 223 Italian, and 148 French). The root mean square error of approximation (RMSEA) and comparative fit index (CFI) indicated model fit. RESULTS: Compared with the 20-item version, the 16-item solution significantly increased the fit (p < 0.001) across all language versions, to achieve good model fit (CFI = 0.96, RMSEA = 0.06). For both 16-item and 20-item models, equivalence across languages was not reached, with some items showing weaker item-loading for some languages, in particular German and French. CONCLUSION: In patients with adolescent idiopathic scoliosis, the shorter 16-item version showed a better fit to the intended 4-factor structure of the SRS-instrument. The wording of some of the items, and/or their equivalence across language versions, may need to be addressed. Questionnaire completion can be a burden for patients; if a shorter, more structurally valid version is available, its use should be encouraged.

Cervical Spinal Cord Degeneration in Spinocerebellar Ataxia Type 7.

BACKGROUND AND PURPOSE: Spinocerebellar ataxia type 7 is an autosomal dominant neurodegenerative disease caused by a cytosine-adenine-guanine (CAG) repeat expansion. Clinically, spinocerebellar ataxia type 7 is characterized by progressive cerebellar ataxia, pyramidal signs, and macular degeneration. In vivo MR imaging studies have shown extensive gray matter degeneration in the cerebellum and, to a lesser extent, in a range of cortical cerebral areas. The purpose of this study was to evaluate the impact of the disease in the spinal cord and its relationship with the patient's impairment. MATERIALS AND METHODS: Using a semiautomated procedure applied to MR imaging data, we analyzed spinal cord area and eccentricity in a cohort of 48 patients with spinocerebellar ataxia type 7 and compared them with matched healthy controls. The motor impairment in the patient group was evaluated using the Scale for Assessment and Rating of Ataxia. RESULTS: Our analysis showed a significantly smaller cord area (t = 9.04, P < .001, d = 1.31) and greater eccentricity (t = -2.25, P =. 02, d = 0.32) in the patient group. Similarly, smaller cord area was significantly correlated with a greater Scale for Assessment and Rating of Ataxia score (r = -0.44, P = .001). A multiple regression model showed that the spinal cord area was strongly associated with longer CAG repetition expansions (P = .002) and greater disease duration (P = .020). CONCLUSIONS: Our findings indicate that cervical spinal cord changes are progressive and clinically relevant features of spinocerebellar ataxia type 7, and future investigation of these measures as candidate biomarkers is warranted.

Motor and sensitive axonal regrowth after multiple intercosto-lumbar neurotizations in a sheep model.

STUDY DESIGN: Experimental animal study. OBJECTIVE: To evaluate motor and sensitive axonal regrowth after multiple intercosto-lumbar neurotizations in a sheep model. SETTING: France. METHODS: Fifteen sheep were separated into three groups. Five sheep had multiple intercosto-lumbar neurotizations and a spinal cord lesion, five sheep were neurotized without any spinal cord lesion and five sheep had a spinal cord lesion without any neurotizations. Six months after the initial surgery, histological study of the neurotized roots was performed. RESULTS: The length of the three rerouted intercostal nerves was sufficient in the 10 sheep to perform an intercosto-lumbar neurotization in good conditions. Eight sheep out of the 15 had postoperative complications responsible for the animal's death in five cases. Histological cross-sections of all the neurotized L2, L3 and L4 roots showed numerous myelinated regenerated axons. Dorsal root ganglions of neurotized roots showed both large and small neurons with normal nucleus and cytoplasm. The fluorescent retrograde labeling of 18 roots revealed labeled motor neurons in five cases. CONCLUSIONS: This study demonstrates the technical feasibility of intercosto-lumbar neurotizations in a big mammalian model. Intercostal nerve harvesting and rerouting was successfully performed in all the cases. Our histological results proved, in all the animals studied, the ability of motor and sensitive neurons to regenerate through the neurotization area. In the context of the future clinical application of strategies aimed at promoting axonal regeneration after severe spinal cord injury, the present data suggest that multiple intercosto-lumbar neurotization could be helpful to promote lower limb muscular strength recovery after spinal cord injuries.

Surface charge and the effect of excess calcium ions on the hydroxyapatite surface.

This paper describes the use of surface titration as a more direct probe of the surface chemistry of hydroxyapatite (HA) than zeta-potential measurements. The variation in HA surface charge with pH for two different KCl electrolyte concentrations was determined titrimetrically and the point of zero charge (PZC) found to be at a pH of 7.3 +/- 0.1. The curves also demonstrated that HA accumulates positive charge more readily below the PZC than it accumulates negative charge above it. Extended titration data indicated that dissolution occurred more rapidly in increasingly acidic conditions, but was inhibited by increasing electrolyte strength. Similar experiments with 2.5 mM Ca(2+) in the electrolyte show that Ca(2+) adsorption balances loss of H(+) to give a near-neutral surface at any pH above 7 (subject to availability of calcium ions and adsorption sites). The mechanism for adsorption has been shown to be deprotonation of adjacent surface HPO(4)(2-) sites and subsequent adsorption of a calcium ion to the lattice surface site. Furthermore, inhibition of dissolution under alkaline conditions in the presence of Ca(2+) suggested that dissolution was driven by desorption of Ca(2+). Modelling of the adsorption/desorption processes demonstrated that in both pure water and under physiological conditions phosphate groups will predominate at the HA surface. Furthermore, the (200) plane was identified as the likely form of the HA surface. These methodologies and findings are particularly relevant to investigation of biological response with respect to modification of surface hydrophobicity and surface energy or charge.

Osteonecrosis in retrieved femoral heads after failed resurfacing arthroplasty of the hip.

We present the histological findings of bone retrieved from beneath the femoral components of failed metal-on-metal hip resurfacing arthroplasties. Of a total of 377 patients who underwent resurfacing arthroplasty, 13 required revision; for fracture of the femoral neck in eight, loosening of a component in three and for other reasons in two. None of these cases had shown histological evidence of osteonecrosis in the femoral bone at the time of the initial implantation. Bone from the remnant of the femoral head showed changes of osteonecrosis in all but one case at revision. In two cases of fracture which occurred within a week of implantation, the changes were compatible with early necrosis of the edge of the fracture. In the remaining six fractures, there were changes of established osteonecrosis. In all but one of the non-fracture cases, patchy osteonecrosis was seen. We conclude that histological evidence of osteonecrosis is a common finding in failed resurfaced hips. Given that osteonecrosis is extensive in resurfaced femoral heads which fail by fracture, it is likely to play a role in the causation of these fractures.

Risk Factors For the Development of a Mobile Degenerative Spondylolisthesis at L4-L5.

OBJECTIVE: The purpose of this study was to identify factors that may be important in determining whether a degenerative spondylolisthesis at L4-L5 is mobile. SUMMARY OF BACKGROUND DATA: Degenerative scoliosis is a common condition among middle-aged and elderly adults. Sacropelvic morphology and orientation modulate the geometry of the lumbar spine and, consequently, the mechanical stresses at the lumbo-sacral junction. To date, no in vivo data exist to describe the relationship between these pelvic parameters and their association with a mobile spondylolisthesis. METHOD: Sixty consecutive patients with a degenerative spondylolisthesis (DS) at L4-L5 with adequate imaging were identified. Patient groups were defined on the basis of whether the DS was mobile (Group A) or nonmobile (Group B) when comparing the upright plain lumbar radiograph to the supine magnetic resonance imaging (MRI). We assessed the grade of slip, lumbar lordosis, pelvic parameters, and facet characteristics (angles, tropism, presents of effusion, degenerative score-cartilage and sclerosis values) as well as disc degenerative score (Pfirrmann) at L4-L5. RESULTS: There were 40 patients in Group A and 20 in Group B. No significant differences were found between groups for pelvic incidence (p = .409), pelvic tilt (p = .476), sacral slope (p = .785), lumbar lordosis (p = .695), degree of facet tropism (p = .38), and magnitude of the facet effusions (p = .01). Facet angle differences between groups approached significance (p = .058). Significant differences between groups were found in cartilage degenerative score (p = .01), facet sclerosis grade (p = .01), and disc degenerative score (p < .0001). In Group A, 10 of 40 (25%) reduced fully and were not apparent on the supine MRI. CONCLUSIONS: Sagittal pelvic parameters do not play a significant role in differentiating between mobile and nonmobile DS at L4-L5. However, DS does appear to be associated with more sagittally orientated facets, higher Pfirrmann grade, and higher facet cartilage and sclerosis degenerative scores.

The Influence of Lumbar Spinal Subtype on Lumbar Intervertebral Disc Degeneration in Young and Middle-Aged Adults.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To identify whether an in vivo correlation exists between lumbar spinal subtype (LSS) and lumbar disc degeneration (LDD) in young adults. SUMMARY OF BACKGROUND DATA: Lumbar disc degeneration has largely been ascribed to biomechanical and structural alterations to the disc, which are attributed to aging and pathological physical loading. Sagittal alignment in the asymptomatic spine has also been considered. A biomechanical study by Roussouly and Pinheiro-Franco proposed level-specific patterns in LDD. To date, no in vivo correlation between the LSS and LDD has been established. METHODS: The authors screened 608 consecutive patients over 5.3 years. Lumbar spinal subtype and pelvic parameters were collected from standing lumbar radiographs and were categorized using the classification of Roussouly and Pinheiro-Franco. Lumbar disc degeneration at all lumbar intervertebral levels was classified using criteria of Pfirrmann et al. A stratified disc degeneration score was derived for each patient. Lumbar disc degeneration in type I, II, and IV LSS was compared using chi-square test. Pelvic incidence was correlated with stratified disc degeneration score using Spearman R, to determine whether a high PI was protective against LDD. Statistical significance was accepted at p < .05. RESULTS: A total of 139 patients were included, with 91 females and a mean age of 32.6 years (range, 13-49 years). For LSS grades I to IV, there were 10 (7.3%), 43 (30.9%), 50 (35.9%), and 36 (25.9%) patients, respectively. The proportion of high-grade (Pfirrmann grades IV and V) LDD increased distally toward the lower intervertebral levels, affecting 2.88%, 2.9%, 5%, 9.4%, 33.1%, and 54% of discs at each sequential lumbar level from T12-L1 to L5-S1, respectively. Age but not gender was statistically significant for higher-grade LDD (p < .0001 and p = .442, respectively). Pelvic incidence across all LSS grades was not significantly correlated with stratified disc degeneration score (Spearman R = 0.0933; p = .335). No LSS (type I-IV) reached statistical significance for a specific pattern of LDD. CONCLUSIONS: In this study, LSS was not statistically significantly correlated with LDD, nor was a high pelvic incidence protective against LDD.

Eflornithine versus cotrimoxazole in the treatment of Pneumocystis carinii pneumonia in AIDS patients.

OBJECTIVES: To compare cotrimoxazole and eflornithine as primary treatment for first-episode Pneumocystis carinii pneumonia (PCP). DESIGN: Prospective open-labelled study. METHODS: Patients were randomized to eflornithine (400 mg/kg daily, as a continuous intravenous infusion) or cotrimoxazole (3.84 g twice daily, intravenously) for 14 days. RESULTS: Only 39% of patients treated with eflornithine (20 out of 51) and 40% of those given cotrimoxazole (nine out of 47) successfully completed therapy. Although 12 out of the 36 patients with confirmed PCP were treated successfully with eflornithine, significantly more patients were withdrawn from the eflornithine group because of therapy failure (25 out of 51 versus 10 out of 47, P = 0.007). This significant difference persisted in patients in whom a diagnosis of PCP was confirmed histologically (19 out of 33 versus seven out of 27, P = 0.03). Significantly more patients were withdrawn from cotrimoxazole because of serious drug-related side-effects (38 versus 12%, P = 0.005). CONCLUSIONS: Eflornithine (400 mg/kg daily) is less effective than cotrimoxazole (7.68 g daily) as treatment for first-episode PCP. Eflornithine does have activity against P. carinii in humans.

The impact of an enteroviral RT-PCR assay on the diagnosis of aseptic meningitis and patient management.

BACKGROUND: Enterovirus (EV) is a major cause of aseptic meningitis and non-specific febrile illness in children. Since the majority of patients are hospitalized for possible bacterial infection, a rapid test for the diagnosis of enteroviral meningitis (EVM) may reduce hospitalizations and unnecessary treatments. OBJECTIVE: To review the impact of an EV reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the diagnosis of EVM on patient management. STUDY DESIGN: CSF from 1056 patients admitted to the hospital between 1998 and 2001 was tested using EV RT-PCR. The results were correlated with CSF counts, diagnosis, test turnaround time (TAT) and length of hospital stay (LOS). RESULTS: EV RT-PCR was positive for 113 patients (11%). Of these cases, 92% occurred during the summer months and 77% were in children <19 years of age. Children <3 years old with EVM frequently had non-specific clinical findings and lacked pleocytosis. There was a significant correlation between decreasing LOS and TAT (r(2)=0.97, P<0.001). CONCLUSION: RT-PCR testing for EVM is an important tool to aid in the diagnosis of children with non-specific febrile illness. This test impacted patient management as measured by shortened patient stays, which should translate into significant health care savings.

A one-step RT-PCR assay using an enzyme-linked detection system for the diagnosis of enterovirus meningitis.

BACKGROUND: Enteroviruses are the most common cause of meningitis in the United States, with an estimated 50000-75000 cases each year. Enteroviral meningitis (EVM) is frequently a diagnosis of exclusion, as viral cultures lack sensitivity and require prolonged incubation periods. OBJECTIVE: To develop a sensitive and rapid test for the diagnosis of EVM. STUDY DESIGN: A rapid, one-step, reverse transcriptase-polymerase chain reaction (RT-PCR) was used in a prospective analysis of 160 patients who had cerebrospinal fluid (CSF) tested for enterovirus. RESULTS: Of the 160 patients, 14 were excluded due to missing CSF viral culture data. A total of 14 were CSF culture positive (10 with pleocytosis) and 19 were PCR positive (15 with pleocytosis). The ability to detect enterovirus by either culture or PCR correlated significantly with the white blood cell count in the CSF (P=0.001). Based on a clinical definition of enterovirus culture positive and pleocylosis: ten had definite EVM and 12 had probable EVM (pleocytosis without any other cause). Four had possible EVM (CSF culture positive without pleocytosis) and 18 had pleocytosis due to other causes. PCR was positive in all ten patients with definite EVM. Five out of 12 patients with probable EVM and three out of four patients with possible EVM. No patients with pleocytosis due to other causes were PCR positive and one patient that was defined as EVM negative (culture negative and no pleocytosis) was PCR positive. Overall, PCR was positive in 18 out of the 26 patients with a likelihood of EVM, while CSF culture was positive in only 14 cases. Our results demonstrated that RT-PCR enhances the sensitivity of enterovirus detection in CSF (69 vs. 54% for culture). CONCLUSION: The diagnosis of EVM is difficult to make clinically: the enhanced sensitivity and rapid turn around time of PCR will be of great clinical benefit.

Teicoplanin: a well-tolerated and easily administered alternative to vancomycin for gram-positive infections in intensive care patients.

A prospective, randomized multicentre study was conducted in order to evaluate the potentially superior tolerability profile of teicoplanin plus netilmicin compared with vancomycin plus netilmicin in patients in ICUs. We considered that these glycopeptides have been shown to have comparable efficacy and that comparative tolerability is of paramount importance, particularly in severely ill patients. A total of 56 patients were enrolled into the study (36 males and 20 females). Twenty-four patients were included in the teicoplanin plus netilmicin group (15 males, 9 females: mean age 56.8 years). The mean simplified acute physiological score (SAPS) was 9.4 (range 4-20). Thirty-two patients were randomized to receive vancomycin plus netilmicin (21 males, 11 females; mean age 56.4 years). The mean SAPS was 9.3 (range 2-16). Septicaemia was the most common infection (14 cases in each group). Most infections were caused by Staphylococcus aureus or coagulase-negative staphylococci. The mean daily doses were: for teicoplanin, 457 mg (6.7 mg/kg); for vancomycin, 1678 mg (24.4 mg/kg); and for netilmicin 263.3 mg (3.9 mg/kg) in the teicoplanin group and 248 mg (3.8 mg/kg) in the vancomycin group. The trough levels of teicoplanin in the serum remained mostly between 7 and 10 mg/l, while more fluctuation was seen in patients receiving vancomycin. The mean trough levels of netilmicin in the serum were 1.2 (SD 0.9) mg/l in the teicoplanin group, compared with 1.7 (SD 1.4) mg/l in the vancomycin group (NS: p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Teicoplanin vs. vancomycin for the treatment of serious infections: a randomised trial.

A prospective, randomised study of 56 patients comparing teicoplanin with vancomycin for suspected or proven severe Grampositive infection was conducted. The majority of infections were soft tissue infections (8 teicoplanin; 16 vancomycin) and by chance a significantly higher number of Hickman catheter-related infections occurred in the vancomycin arm (4 vs. 14, P < 0.01). Teicoplanin was administered as a single daily dose of 400 mg iv or im; 5 patients received 200 mg following the initial dose of 400 mg. Vancomycin was given 1 g every 12 h. Fifty-four patients were evaluable for efficacy (26 teicoplanin, 28 vancomycin). Of these, 18 episodes in 17 patients (teicoplanin) and 19 episodes in 18 patients (vancomycin) gave an evaluable clinical response, the success rates being similar (76% teicoplanin; 68% vancomycin). Staphylococcus aureus was the most common pathogen isolated; all pathogens were susceptible to both glycopeptides with MICs < 4 mg/l. Bacteriological elimination rates were similar in both groups (71% teicoplanin; 78% vancomycin). Significantly more patients given vancomycin experienced adverse events (7 teicoplanin; 16 vancomycin; P = 0.03). This caused treatment to be discontinued in 4 cases, compared with only one receiving teicoplanin. The most common vancomycin-related events were histamine-associated reactions (15 patients), including 2 cases of Red Man Syndrome, and nephrotoxicity (5 patients). There were no histamine-mediated events and only one case of nephrotoxicity with teicoplanin. Teicoplanin and vancomycin show similar clinical and bacteriological efficacy and teicoplanin is significantly less toxic and easier to use in patients with severe infection.

The Nearchus project: antibiotic susceptibility of respiratory pathogens and clinical outcome in lower respiratory tract infections at 27 centres in the UK.

Community-acquired respiratory infections are usually treated empirically by the primary care physician. Increasing antibiotic resistance, for example, in pneumococci, prompted a UK survey of antibiotic susceptibility of three major lower respiratory tract pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Each of 27 centres was asked to collect up to 100 isolates of the three species and submit them for confirmation of identity and for susceptibility testing to a central laboratory. In addition, general practitioners were asked for demographic details on the patient, their treatment and the clinical outcome. Of 1689 viable pathogens collected, there were 1078 (64%) strains of H. influenzae, 258 (15%) of M. catarrhalis and 353 (21%) of S. pneumoniae. Production of beta-lactamase was detected in 163 (15%) of 1078 isolates of H. influenzae and in 243 (94%) isolates of M. catarrhalis. For S. pneumoniae, moderate resistance to penicillin (MIC 0.12-1 mg/l) was found in 12 (3.4%) isolates and high level resistance (MIC > or = 2 mg/l) in 13 (3.7%) isolates. The most common individual treatments were amoxycillin, amoxycillin/clavulanate (amoxyclav) , and erythromycin. Complete or partial clinical resolution was achieved in 88% of 809 patients infected with H. influenzae, 83% of 197 infected with M. catarrhalis and 90% of 255 infected with S. pneumoniae.

A comparison of teicoplanin versus cephradine plus metronidazole in the prophylaxis of post-operative infection in vascular surgery.

A total of 272 patients were enrolled into this prospective, unblinded, randomized comparison of single-dose teicoplanin vs three doses of cephradine plus metronidazole as prophylaxis for vascular surgery at St James's and Seacroft Hospitals, Leeds, UK. In all, 71.3% of patients (194/272) were enrolled at St James's University Hospital. Patients received either a single dose of teicoplanin, 6 mg/kg i.v., or cephradine, 1 g i.v. with metronidazole, 1 g rectally, at induction of anaesthesia followed by two further 1 g doses of cephradine and metronidazole 8 and 16 hours later. There were 136 patients in each treatment group. The most common operations were femoropopliteal grafts (96) and aortic aneurysm repairs (47). In the 'intention-to-treat' analysis, primary wound infections were seen in 4.4% of patients (6/136) receiving teicoplanin and 5.9% of patients (8/136) receiving cephradine plus metronidazole (95% CI -6.7%, +3.8%). Other disturbances to wound healing occurred in 23 patients (11 in the teicoplanin and 12 in the cephradine plus metronidazole group). Secondary respiratory tract infections occurred in 17 patients (8 receiving teicoplanin and 9 receiving cephradine plus metronidazole). In the evaluable patients analysis, primary wound infections occurred in 3.5% of patients (4/114) receiving teicoplanin and 5.1% of patients (6/117) receiving cephradine plus metronidazole. Staphylococcus aureus and Proteus sp. were the most common pathogens in primary wound infections. Despite the absence of Gram-negative cover in the teicoplanin group, Gram-negative infections occurred more often in the cephradine plus metronidazole group. Surgery of the lower extremities carried the highest risk of post-operative infection. Rates of infection were significantly higher at Seacroft Hospital (P = 0.001), and significantly higher for cephradine plus metronidazole between the two hospitals (P = 0.0008). Adverse events occurred in 40 patients receiving teicoplanin (29.4%) and 39 patients receiving cephradine plus metronidazole (28.7%). In 19 patients receiving teicoplanin (14%) and 15 receiving cephradine plus metronidazole (11%) these events were considered to be related to the study drugs. The most often reported events were infections, cardiac events and vascular phenomena (haematoma or emboli). Marked changes in haematological parameters and liver function tests were noted seven days after operation in patients in each treatment group, but these resolved quickly as the effects of the operation subsided. ESR remained elevated in both groups at the six-month follow-up assessment. It is concluded from this two-centre study that a single dose of teicoplanin shows similar efficacy to a three-dose regimen of cephradine plus metronidazole as prophylaxis for wound infection in vascular surgery. Both regimens were well tolerated, and there was an equal incidence of adverse events in the two regimens, which reflected the poor general health status of this elderly study population.

Infective endocarditis and glycopeptides.

BACKGROUND: Despite the number of antibacterial agents currently available, endocarditis remains a difficult disease to treat and the mortality rate has not fallen in recent years. The glycopeptides have good activity against the Gram-positive bacteria commonly implicated in endocarditis (staphylococci, both coagulase-positive and negative; enterococci and streptococci). OBJECTIVES: To assess the impact of the glycopeptides vancomycin and teicoplanin on the therapy of infectious endocarditis caused by Gram-positive bacteria. METHODS: A retrospective review of all major published or recently conducted studies using vancomycin or teicoplanin to treat endocarditis. RESULTS: Cure rates obtained with vancomycin and teicoplanin are similar, but there are no controlled studies to investigate this. Vancomycin nephrotoxicity limits its use in endocarditis, in particular when used in combination with an aminoglycoside. By contrast, teicoplanin shows little nephrotoxic potential, even in patients with some degree of renal impairment or when given in combination with an aminoglycoside. Teicoplanin should be used at doses of 6 mg/kg/day or higher to achieve satisfactory cure rates. CONCLUSIONS: Clinical data on the use of glycopeptides in endocarditis suffer from a lack of controlled trials. Although teicoplanin appears to offer some advantages over vancomycin in the therapy of endocarditis, there is an urgent need for randomized, clinical trials before definitive conclusions can be drawn.

Fluoroquinolones: is there a different mechanism of action and resistance against Streptococcus pneumoniae?

Starting in the 1950s, study and elucidation of the biochemical mechanisms of resistance to antibiotics led to the understanding of both the biology of bacteria and the mode of action of antibiotics. This holds true for the relationship between Streptococcus pneumoniae and the fluoroquinolones. A new feature in this approach is the availability of the nearly complete chromosome sequence of this major human pathogen. In S. pneumoniae, resistance appears to be mainly due to mutational alterations in the intracellular targets of the fluoroquinolones, the type II DNA topoisomerase gyrase and topoisomerase IV. Both enzymes appear to be the primary targets of the drugs in this species. Mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene or the parC gene, which encode the A subunits of DNA gyrase and topoisomerase IV respectively, confer resistance to single-step mutants. Mutations in gyrB and parE, which encode the B subunits of DNA gyrase and topo IV, respectively, have also been implicated in the fluoroquinolone resistance of certain mutants obtained in vitro. The antibiotics most affected by a single mutation are those for which the mutation occurs in their preferred target e.g. gyrase for sparfloxacin and gatifloxacin and topo IV for ciprofloxacin and levofloxacin. The activity of all fluoroquinolones is decreased further when two or more mutations are present. Because they possess similar targets of action, there is cross resistance, albeit at various degrees depending on the intrinsic activity of the molecule, among fluoroquinolones. This stresses, once more, the misleading concept of breakpoints for clinical categorization. A second mechanism of resistance, enhanced active efflux of hydrophilic quinolones such as norfioxacin and ciprofloxacin, is mediated by the membrane-associated protein, PmrA (pneumococcal multidrug resistance). This protein is a 12-transmembrane segment proton-dependent multidrug efflux pump of the major facilitator family. The combinatorial approach of bacteria to fluoroquinolone resistance implies that the molecule actually used, as well as a less active member of the class that is more apt to detect resistance mechanisms (e.g. ciprofloxacin), should be tested in vitro.