Suppressive antibiotic therapy in prosthetic joint infections: a multicentre cohort study.

OBJECTIVES: The aim was to describe the effectiveness of suppressive antibiotic treatment (SAT) in routine clinical practice when used in situations in which removal of a prosthetic implant is considered essential for the eradication of an infection, and it cannot be performed. METHODS: This was a descriptive retrospective and multicentre cohort study of prosthetic joint infection (PJI) cases managed with SAT. SAT was considered to have failed if a fistula appeared or persisted, if debridement was necessary, if the prosthesis was removed due to persistence of the infection or if uncontrolled symptoms were present. RESULTS: In total, 302 patients were analysed. Two hundred and three of these patients (67.2%) received monotherapy. The most commonly used drugs were tetracyclines (39.7% of patients) (120/302) and cotrimoxazole (35.4% of patients) (107/302). SAT was considered successful in 58.6% (177/302) of the patients (median time administered, 36.5 months; IQR 20.75-59.25). Infection was controlled in 50% of patients at 5 years according to Kaplan-Meier analysis. Resistance development was documented in 15 of 65 (23.1%) of the microbiologically documented cases. SAT failure was associated with age <70 years (sub-hazard ratio (SHR) 1.61, 95% CI 1.1-2.33), aetiology other than Gram-positive cocci (SHR 1.56, 95% CI 1.09-2.27) and location of the prosthesis in the upper limb (SHR 2.4, 95% CI 1.5-3.84). SAT suspension was necessary due to adverse effects in 17 of 302 patients (5.6%). CONCLUSIONS: SAT offers acceptable results for patients with PJI when surgical treatment is not performed or when it fails to eradicate the infection.

Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study.

It is important to know the spectrum of the microbial aetiology of prosthetic joint infections (PJIs) to guide empiric treatment and establish antimicrobial prophylaxis in joint replacements. There are no available data based on large contemporary patient cohorts. We sought to characterize the causative pathogens of PJIs and to evaluate trends in the microbial aetiology. We hypothesized that the frequency of antimicrobial-resistant organisms in PJIs has increased in the recent years. We performed a cohort study in 19 hospitals in Spain, from 2003 to 2012. For each 2-year period (2003-2004 to 2011-2012), the incidence of microorganisms causing PJIs and multidrug-resistant bacteria was assessed. Temporal trends over the study period were evaluated. We included 2524 consecutive adult patients with a diagnosis of PJI. A microbiological diagnosis was obtained for 2288 cases (90.6%). Staphylococci were the most common cause of infection (1492, 65.2%). However, a statistically significant rising linear trend was observed for the proportion of infections caused by Gram-negative bacilli, mainly due to the increase in the last 2-year period (25% in 2003-2004, 33.3% in 2011-2012; p 0.024 for trend). No particular species contributed disproportionally to this overall increase. The percentage of multidrug-resistant bacteria PJIs increased from 9.3% in 2003-2004 to 15.8% in 2011-2012 (p 0.008), mainly because of the significant rise in multidrug-resistant Gram-negative bacilli (from 5.3% in 2003-2004 to 8.2% in 2011-2012; p 0.032). The observed trends have important implications for the management of PJIs and prophylaxis in joint replacements.

Clinical validation of a multiplex real-time PCR assay for detection of invasive candidiasis in intensive care unit patients.

BACKGROUND: New techniques, such as those based on multiplex quantitative real-time PCR (MRT-PCR), can improve the detection of invasive candidiasis (IC). METHODS: We prospectively studied 63 intensive care unit patients with suspected IC and 40 healthy controls. Blood cultures and MRT-PCR were performed at day 0 and +2, +7, +14 and +21 days in all patients. In addition, ß-d-glucan (BDG) and Candida albicans germ tube antibody (CAGTA) were quantified. RESULTS: IC was confirmed in 27 patients. Colonization was significantly higher in patients with IC (96% versus 64%, P = 0.002). The sensitivity, specificity, positive predictive value and negative predictive value of MRT-PCR for the diagnosis of IC were 96.3%, 97.3%, 92.8% and 98.7%, respectively. The positive predictive value and specificity were significantly higher for MRT-PCR than for BDG and CATGA. MRT-PCR performed very well, especially in deep-seated IC (sensitivity 90.9% versus 45.4% for blood culture; P = 0.06). As regards the most appropriate clinical sample for DNA amplification, in this study whole blood and serum presented similar results. CONCLUSIONS: MRT-PCR appears to be a useful test for confirming a diagnosis of IC in critically ill patients, especially in those with deep-seated disease. Its high sensitivity and positive predictive value make it a much more efficient tool for the management of IC than other diagnostic procedures and clinical scores.

Emerging trends in candidemia: a higher incidence but a similar outcome.

The clinical presentation and outcome of candidemia has changed in recent years. We compared two 5-year periods (2000-2004 and 2005-2009) in a single institution. We recorded 419 candidemia episodes during the study period (124 in the first period and 295 in the second period). We observed a significant increase in the number of cases per 1000 admissions per year, from 0.57 in 2000 to 1.52 in 2009 (χ(2) LT <0.001). Candida albicans was the most frequently isolated species (42.2%), followed by Candida parapsilosis (34.4%) and Candida glabrata (12.9%). In the second period, episodes were associated with higher comorbidity and were more commonly nosocomial, with a more frequent catheter-related source and an increased rate of C. glabrata infection. No significant differences were observed in susceptibility by species during the study period. According to multivariate analysis, the independent factors associated with higher mortality were shock, age >50 years, elevated comorbidity score (Charlson index >6), and source of candidemia other than catheter. In contrast to the increase in comorbid conditions observed in recent years, mortality remained similar during both periods (~37% during the first month). This finding could be attributed to a significant increase in catheter-related candidemia and better outcome, as well as to a potential improvement in the management of antifungal therapy in recent years.

Axon-glia interactions and the domain organization of myelinated axons requires neurexin IV/Caspr/Paranodin.

Myelinated fibers are organized into distinct domains that are necessary for saltatory conduction. These domains include the nodes of Ranvier and the flanking paranodal regions where glial cells closely appose and form specialized septate-like junctions with axons. These junctions contain a Drosophila Neurexin IV-related protein, Caspr/Paranodin (NCP1). Mice that lack NCP1 exhibit tremor, ataxia, and significant motor paresis. In the absence of NCP1, normal paranodal junctions fail to form, and the organization of the paranodal loops is disrupted. Contactin is undetectable in the paranodes, and K(+) channels are displaced from the juxtaparanodal into the paranodal domains. Loss of NCP1 also results in a severe decrease in peripheral nerve conduction velocity. These results show a critical role for NCP1 in the delineation of specific axonal domains and the axon-glia interactions required for normal saltatory conduction.

A theoretical four-compartment model to evaluate separate kidney technetium-99m-MAG3 kinetics in humans.

BACKGROUND: Pharmacokinetic modeling based on compartmentalization has provided a valuable tool to assess the clearance patterns of various glomerular and tubular agents. However, no models have been proposed thus far that combine vascular data and imaging data in order to gain a deeper knowledge on renal pathophysiology, and to obtain more diagnostic information of clinical relevance. To this aim, we propose a four-pool model for the evaluation of separate renal function. METHODS: In a group of ten normal volunteers and twenty patients with various renal diseases, we tested the four-pool model based on the identification of the two kidneys as two distinct pools. This approach made it possible to integrate the separate kidney contributions deriving from in vivo imaging data, and allows the researcher to quantitate many parameters specific to each kidney. RESULTS: The parameters TERR, TERL, MRTR, MRTL, vR, vL, k3R-1, K3L-1 permit the normal from abnormal states of renal function to be differentiated, as well as monolateral from bilateral renal disease to be separated within the abnormal function group. CONCLUSIONS: The proposed approach combines the advantages of plasma clearance methods with those derived by gamma-camera imaging, and makes it possible to quantitate the differential renal function. This feature may be clinically relevant in renal transplant donors, where full knowledge of renal pathophysiology could guide the procedure.

Simultaneous estimation of glomerular filtration rate and renal plasma flow.

UNLABELLED: Comparing the measurements of both glomerular filtration (GFR) and tubular excretion rates [TER(MAG3)] by multi-sample and single-sample methods has been performed after a single bolus injection of 3.7 MBq 51Cr-EDTA plus 37 MBq 99mTc-MAG3. METHODS: We studied 17 healthy volunteers and 28 patients with a wide range of renal function. For each plasma clearence curve, nine plasma samples were drawn at intervals from 10 to 240 min after injection of tracers. When comparing individual values for GFR and TER (MAG3) from the tracer dilution spaces (VD) with those derived from the analysis of the entire plasma disappearance curves of two radiopharmaceuticals, a good linear correlation appears (r = 0.96). RESULTS: We found that the nadir-error (Sy,x) for predicted GFR occurs at 180 min (11.0 ml/min/1.73 m2), while the nadir-error for predicted TER (MAG3) is reached at 90 min (26.4 ml/min/1.73 m2). CONCLUSION: In the computation of GFR and TER (MAG3) with a single-sample method, it appears that the mean residence time (t) for each tracer represents the optimum plasma sampling time. Our results suggest that the single injection of 51Cr-EDTA and 99mTc-MAG3 followed by blood sampling twice permits accurate simultaneous estimation of GFR and TER (MAG3) and, after correction of the latter kinetic parameter, effective renal plasma flow.

Full-blown hypothyroidism associated with vitiligo and acropachy. Report of one case.

During the first two years after the onset of hypothyroidism, a patient with spontaneous primary myxedema developed thyroid acropachy. Fifteen years before the diagnosis of thyroid disease, he had patchy vitiligo of the face. There were high serum levels of antibodies against thyroglobulin (anti-Tg) and microsomal antigen (anti-M) were present, while the serum levels of antibodies against the second antigen of the colloid and the cell-surface antigen fell within the normal range. Moreover, antibodies to gastric parietal cells, adrenocortical cells or pancreatic islets in the serum were not present. Concerning the immuno-genetic pattern of our patient, his HLA system did not appear to confirm the well documented prevalence in whites with autoimmune disorders of an antigen specificity positive for the locus DR3.

A theoretical five-pool model to evaluate triiodothyronine distribution and metabolism in healthy subjects.

We have examined the in vivo production, distribution, metabolism, and excretion of radiolabeled triiodothyronine (T3) in eight normal humans using a new five-pool mammillary model which includes four extravascular pools to represent liver, kidney, skeletal muscle, and all other unquantified tissues. Trace amounts of [125I]T3 and [131I]T3 were injected and plasma, stool and urine samples and external counting of liver, kidney, and thigh were drawn following bolus injection of radiolabeled T3. Our results indicate that the skeletal muscle pool represents the largest pool in our system, being 42% of the total-body pool size of the hormone (Qtot = 0.52 +/- 10% [CV] micrograms/kg body weight [BW]). The plasma pool QA (0.090 +/- 9% [CV] micrograms/kg BW) contains approximately 17% of Qtot, while the size of the unquantified tissue pool QE (0.150 +/- 16% [CV] micrograms/kg BW) is approximately 29% of Qtot. Furthermore, the size of liver pool QB and the size of kidney pool QC are about 10% and 2%, respectively, of Qtot. The rate of T3 metabolized in the skeletal muscle pool and in the unquantified composite tissue pool, as a sum, represents approximately 53% of the plasma appearance rate of the hormone (PAR3), while the rate of T3 metabolized in the liver and kidney pools represents 27% and 3% of PAR3, respectively. The rate of T3 excreted via feces and urine, as a sum, accounts for about 20% of PAR3.(ABSTRACT TRUNCATED AT 250 WORDS)

Multicompartmental analysis of triiodothyronine (T3) distribution and metabolism in clinically euthyroid obese individuals.

Triiodothyronine (T3) kinetic studies were performed on ten clinically non-fasting euthyroid obese individuals and on eight normal subjects. Kinetic analysis was carried out according to a three-pool model whose basic approach involved the acquisition of data from both vascular and extravascular sources. The former were represented by the plasma disappearance curves of iv injected radiolabeled T3. The latter included fecal and urinary losses and liver, kidney and thigh uptake. A detailed comparison of the T3 kinetics of obese and normal individuals did not uncover many differences between these two groups in the way the hormone is distributed, metabolized and excreted. The mean value for the plasma equivalent distribution volume of T3(VD3) in obese individuals (27.05 L) was not significantly different from that in controls (24.60 L) nor were significant differences observed between the mean value for the plasma appearance rate of the hormone (PAR3) in obese subjects (29.80 micrograms/day) and that in controls (30.05 micrograms/day). The mean value for the size of the slow pool (Qc), including fatty tissue as well as skeletal muscle, was unchanged in obese individuals when compared with controls, although in the obese subjects the mean value for the mass of fatty tissue was about 5 times greater. In addition, in obese individuals, the mean value for the fractional rate transfer from plasma to the slow pool (Kca), which was 9.06 day-1, did not significantly differ from that in controls (9.22 day-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of calculated and measured free thyroid hormones in serum in health and in abnormal states.

To evaluate a theoretical model for calculating free thyroid hormones, based on the law of mass action, we compared values for both calculated and measured free thyroxin and free triiodothyronine in a group of normal subjects. To determine whether the concentrations of circulating free hormones were also predictable from equilibrium considerations in abnormal states, we compared calculated and measured free thyroid hormone values in an additional population including pregnant women and hyperthyroid, hypothyroid, and "sick euthyroid" patients. Predictions based on the model were accurate in all these states except pregnancy, where there was some discrepancy between calculated and measured values for both hormones. In pregnant women with large abnormalities in thyroid-hormone-binding proteins, euthyroidism was accompanied by significantly lower free hormone concentrations, leading us to conclude that, in pregnancy, equilibrium may be reached at concentrations lower than those in other healthy subjects. Values for calculated and measured free thyroid hormones in "sick euthyroids" showed no discrepancy; however, we cannot exclude the possibility that non-dialyzable compounds are present that interfere with the hormone-protein binding.