Very low serum IGF-1 levels are associated with vertebral fractures in adult males with beta-thalassemia major.

PURPOSE: Patients with beta-thalassemia major (BTM) often develop several endocrine disorders due to chronic iron overload. They are also prone to osteoporosis and vertebral fractures. Plasmatic insulin-like growth factor-1 (IGF-1) levels are often low in subjects with BTM, which origin is multifactorial. The aim of this study was to evaluate a possible relationship between serum IGF-1 levels and the presence of osteoporosis and/or vertebral fractures. METHODS: We retrospectively evaluated the occurrence of vertebral fractures in 30 adult male patients affected by BTM (mean age 43.3 ± 7.9 years) with low serum IGF-1 (median value 52.4 ng/ml, 38.5-83.4). Only 6 of them (20.0%) were diagnosed with GH deficiency (GHD) after GHRH/arginine stimulation test, while 23 (76.7%) had osteoporosis and 12 (40.0%) had known vertebral fractures. All patients except one also showed at least one endocrine disorder. RESULTS: Serum IGF-1 was significantly lower in BTM patients with vertebral fractures compared to patients without vertebral fractures (U = 41.0, p = 0.005) while it was not significantly different between patients with low bone mass compared to patients without low bone mass. The diagnosis of GHD was significantly associated with lower serum IGF-1 (p = 0.001) and vertebral fractures (p = 0.002) but not with low bone mass. After ROC analysis, we found that very low IGF-1 (≤ 50.0 ng/dl) was associated with vertebral fractures (sensitivity 83.3%, specificity 75.0%) and was also predictive of GHD (sensitivity 75.0%, specificity 100.0%). CONCLUSION: Our study shows that, in male patients with BTM, serum IGF-1 ≤ 50.0 ng/dl is a marker of vertebral fractures and it is predictive of a diagnosis of GHD.

Efficacy, feasibility and tolerability of ketogenic diet for the treatment of poor response to bariatric surgery.

PURPOSE: Poor response to bariatric surgery, namely insufficient weight loss (IWL) or weight regain (WR), is a critical issue in the treatment of obesity. The purpose of our study was to assess the efficacy, feasibility, and tolerability of very low-calorie ketogenic diet (VLCKD) for the management of this condition. METHODS: A real-life prospective study was conducted on twenty-two patients who experienced poor response after bariatric surgery and followed a structured VLCKD. Anthropometric parameters, body composition, muscular strength, biochemical analyses, and nutritional behavior questionnaires were evaluated. RESULTS: A significant weight loss (mean 14.1 ± 4.8%), mostly due to fat mass, was observed during VLCKD with the preservation of muscular strength. The weight loss obtained allowed patients with IWL to reach a body weight significantly lower than that obtained at the post-bariatric surgery nadir and to report the body weight of patients with WR at the nadir observed after surgery. The significantly beneficial changes in nutritional behaviors and metabolic profiles were observed without variations in kidney and liver function, vitamins, and iron status. The nutritional regimen was well tolerated, and no significant side effects were detected. CONCLUSION: Our data demonstrate the efficacy, feasibility, and tolerability of VLCKD in patients with poor response after bariatric surgery.

Comparison of BACTEC™ blood culture media for the detection of fungemia.

The aim of the present study was to investigate whether addition of the BACTEC™ Mycosis bottle to the standard BACTEC™ aerobic and anaerobic bottles contributed to a higher detection rate and a faster time to detection (TTD) of fungi. This was a retrospective cohort study of all patients with a positive blood culture with Candida species delivered to the Department of Clinical Microbiology, Herlev and Gentofte Hospital, Denmark in the 8-year period 2006 through 2014. The patients had at least one BACTEC™ aerobic and one Mycosis bottle sampled at the same time and at least one of the bottles yielded growth of fungi. Among 184 patients included, 173 were examined using BACTEC™ aerobic, anaerobic and Mycosis bottles. The anaerobic vial generally had the lowest detection rate and the longest TTD. The detection rate of BACTEC™ aerobic plus anaerobic with the BACTEC™ Mycosis bottle was significantly higher than the detection rate of BACTEC™ aerobic plus anaerobic without BACTEC™ Mycosis bottle for all species after 1-5 days, and specially for Candida glabrata at 2, 3, 4 and 5 days. TTD for C. glabrata was significantly shorter for BACTEC™ Mycosis than TTD for BACTEC™ aerobic or anaerobic bottles after ½ to 4 days. When combining "first or only" detection, the BACTEC™ Mycosis bottle had a significantly higher detection as compared to the aerobic bottle. Addition of the BACTEC™ Mycosis bottle to the standard BACTEC™ aerobic and anaerobic bottles significantly contributed to a higher detection rate and a faster TTD of fungemia.

Association of autoimmune thyroid diseases, chronic atrophic gastritis and gastric carcinoid: experience from a single institution.

PURPOSE: Autoimmune polyendocrine syndromes (APS) type III are characterized by the association of autoimmune thyroid disease (ATD) with other autoimmune diseases such as diabetes, alopecia, pernicious anemia, vitiligo and chronic atrophic gastritis. A strong association between ATD and atrophic gastritis (AG) has been demonstrated. Moreover 10 % of patients affected by AG have a predisposition to develop gastric carcinoid and adenocarcinoma as a result of chronic hypergastrinemia caused by achlorhydria and subsequent ELC cells neoplastic transformation. METHODS: The aim of the study is to evaluate, in a consecutive series of patients followed for ATD in our outpatients clinic, the prevalence of AG. In the period 2004-2014, 242 patients with ATD underwent a screening performing APCA, Vitamin B12, ferritin, iron, and hemoglobin and red cells count measurements with subsequent gastroscopy in case of APCA positivity. RESULTS: We found 57/242 (23.5 %) patients with APCA positivity. Of these patients 33/57 (57.8 %), 31 F and 2 M, were affected by Graves disease; 24/57 (42.1 %) 21 F and 3 M by Hashimoto thyroiditis; 10/57 (17.5 %) presented with anemia, 14/57 (24.5 %) with vitamin B12 deficiency, 9/57 (15.7 %) with iron deficiency. In 2/57 a gastric carcinoid was found. CONCLUSIONS: Our data confirm the high association rate of AG in ATD which frequently is not an isolated disease but configure the picture of APS type III and need to be followed accordingly. An early diagnosis may be useful for diagnosis of gastric carcinoids and to explain and treat a gastric related L-thyroxine malabsorption and presence of chronic unexplained anemia.

Randomized clinical trial of prevention of seroma formation after mastectomy by local methylprednisolone injection.

BACKGROUND: Seroma formation, the most prevalent postoperative complication after mastectomy, is an inflammatory process that is potentially preventable via local steroid administration. This study investigated the effect of local steroid administration on seroma formation. METHODS: This was a double-blind randomized placebo-controlled intervention study of a single dose of 80 mg methylprednisolone versus saline on seroma formation after mastectomy. Patients were further classified according to the surgical axillary procedure: mastectomy with sentinel lymph node biopsy (M + SLNB) or mastectomy with level I-II axillary lymph node dissection (M + ALND). Treatments were administered into the wound cavity via the drain orifice following removal of the drain on the first day after surgery. The primary endpoint was seroma formation; secondary endpoints included the frequency of side-effects and complications. RESULTS: A total of 212 women scheduled for mastectomy for primary breast cancer were included. After M + SLNB, 32 (46 per cent) of 69 women developed a seroma in the methylprednisolone group, compared with 52 (78 per cent) of 67 in the saline group (P < 0.001). The mean cumulative seroma volume in the intention-to-treat population for the first 10 and 30 days was significantly lower in the methylprednisolone group (24 ml versus 127 ml in the saline group, and 177 versus 328 ml respectively) (P < 0.001). After M + ALND, similar proportions of patients developed a seroma in the methylprednisolone (35 of 37, 95 per cent) and saline (34 of 36, 94 per cent) groups, and methylprednisolone administration had no significant effect on seroma formation. No differences in infection rate were observed. CONCLUSION: Methylprednisolone administered into the wound cavity on the first day after M + SLNB exerted a highly significant preventive effect against seroma formation during the next 30 days. This effect was not seen in the M + ALND group. Future studies may clarify whether higher or repeated methylprednisolone doses increase the efficacy.

Evaluating antibiotic stewardship programs in patients with bacteremia using administrative data: a cohort study.

When introducing new antibiotic guidelines for empirical treatment of bacteremia, it is imperative to evaluate the performance of the new guideline. We examined the utility of administrative data to evaluate the effect of new antibiotic guidelines and the prognostic impact of appropriate empirical treatment. We categorized 2,008 adult patients diagnosed with bacteremia between 2010 and 2012 according to whether they received cephalosporins or fluoroquinolones (old regimen) or not (new regimen). We used administrative data to extract individual level data on mortality, readmission, and appropriateness of treatment, and computed adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for 30-day mortality and post-discharge readmission by regimen and appropriateness of treatment. In total, 945 (47.1%) were treated by the old regimen and 1,063 (52.9%) by the new. The median length of stay (8 days) did not differ by regimen and neither did the proportion of those receiving appropriate empirical treatment (84.1% vs. 85.5%). However, fewer patients with the new regimen were admitted to the intensive care unit (ICU; 3.8% vs. 12.0%) and they had lower 30-day mortality (16.4% vs. 23.4%). The adjusted 30-day mortality HR for appropriate versus inappropriate treatment was 0.79 (95% CI 0.62-1.01) and 0.83 (95% CI 0.66-1.05) for the new versus the old regimen. The HR for 30-day readmission for appropriate versus inappropriate treatment was 0.91 (95% CI 0.73-1.13) and 1.05 (95% CI 0.87-1.25) for the new versus the old regimen. This study demonstrates that administrative data can be useful for evaluating the effect and quality of new bacteremia treatment guidelines.

Linezolid as rescue treatment for left-sided infective endocarditis: an observational, retrospective, multicenter study.

The increasing number of resistant bacterial strains in infective endocarditis (IE) emphasizes the need for a constant development of antimicrobials. Linezolid is an oxazolidinone with an effect on Gram-positive cocci. Only a few casuistic reports describe its utilization in the treatment of IE. The objective of this study is to report our experience with linezolid from a large consecutive cohort of IE patients. In a retrospective cohort study, data on 550 consecutive IE patients were collected at two tertiary University Hospitals in Copenhagen, Denmark. The main endpoints were differences in the in-hospital and 12 months post-discharge mortality between IE patients receiving linezolid for a part of the treatment and IE patients receiving conventional treatment. Of the 550 patients enrolled in the study, 38 patients received linezolid treatment and 512 received conventional treatment. Reasons for adding linezolid were antibiotic intolerance (n = 13), nephrotoxicity (n = 5), pharmaceutical interactions (n = 1), inadequate clinical response (n = 14), or inadequate microbial response (n = 5). No significant differences in the cure rate (74 % vs. 71 %, p > 0.05), in-hospital mortality (13 % vs. 14 %, p > 0.05), or post-discharge mortality at 12 months follow-up (26 % vs. 26 %, p > 0.05) were observed. In the current study, we found that linezolid, in general, was well tolerated and associated with the same outcome as in patients with Gram-positive IE treated with other antibiotics.

Association of TCF7L2 gene variants with low GAD autoantibody titre in LADA subjects (NIRAD Study 5).

AIMS: We previously demonstrated the presence of two different populations among adult-onset autoimmune diabetes (latent autoimmume diabetes of adults; LADA) having high or low titre of antibodies to glutamic acid decarboxylase (GADA). The transcription factor 7-like 2 (TCF7L2) gene has been recognized as the major gene associated with Type 2 diabetes. The aim of the present study was to evaluate whether the phenotypic heterogeneity of LADA based on GADA titre is associated with TCF7L2 polymorphisms. METHODS: Two hundred and fifty patients identified as LADA, divided into two subgroups with low (< or = 32 arbitrary units) or high (> 32 units) GADA titre, 620 subjects with Type 2 diabetes [from the Non-Insulin Requiring Autoimmune Diabetes (NIRAD) study cohort of 5330 subjects] in addition to 551 consecutive cases of Type 1 diabetes and 545 normoglycaemic subjects were analysed for the rs12255372 and rs7903146 polymorphisms of the TCF7L2 gene using Taqman. RESULTS: The genotype and allele distributions of the two polymorphisms revealed similar frequencies in subjects with low GADA titre and Type 2 diabetes. High GADA titre, Type 1 diabetes and controls also showed comparable frequencies. A significant increase of GT/TT genotypes of the rs12255372 single-nucleotide polymorphism (SNP) and CT/TT genotypes of the rs7903146 SNP was observed in low GADA titre and Type 2 diabetes compared with high GADA titre, Type 1 diabetes and controls (P < or = 0.04 for both comparisons). The risk alleles of both variants were increased in low GADA titre and Type 2 diabetes compared with high GADA titre, Type 1 diabetes and control subjects (P < 0.02 for all comparisons). CONCLUSIONS: TCF7L2 common genetic variants of susceptibility are associated only with low GADA antibody titre in LADA patients.

Healing of chronic necrobiosis lipoidica lesions in a type 1 diabetic patient after pancreas-kidney transplantation: a case report.

Necrobiosis lipoidica (NL) is a degenerative disease of dermal connective tissue of unknown etiology characterized by erythematous plaques preferentially localized to distal extremities. Skin lesions show a chronic relapsing nature. NL is often associated with diabetes mellitus and satisfactory treatment options are lacking. We describe the spontaneous healing of NL lesions after pancreas and kidney transplantation in a Type 1 diabetic patient with chronic NL recalcitrant to a variety of standard treatments. The 31-yr-old male patient had experienced NL lesions for more than 15 yr; despite various systemic and topical treatments, the skin lesions had pregressively enlarged. Because of end-stage renal disease, a simultaneous pancreas and kidney transplantation was performed and immunosuppressive therapy with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisone was started. Pancreatic transplantation maintained satisfactory metabolic control with no need of exogenous insulin. After transplantation, skin lesions slowly healed without any specific treatment, leaving residual areas of fibrotic scars. A skin biopsy confirmed the absence of typical NL lymphocytic and histiocytic inflammatory response. Clinical remission of NL lesions may probably be explained by the concomitant effect of multiple-drug regimen for immunosuppression (TAC, MMF, and prednisone) and improved skin microcirculation secondary to the good metabolic control provided by pancreas transplantation.

Antibiotic treatment and mortality in patients with Listeria monocytogenes meningitis or bacteraemia.

Invasive Listeria monocytogenes infections carry a high mortality despite antibiotic treatment. The rareness of the infection makes it difficult to improve antibiotic treatment through randomized clinical trials. This observational study investigated clinical features and outcome of invasive L. monocytogenes infections including the efficacy of empiric and definitive antibiotic therapies. Demographic, clinical and biochemical findings, antibiotic treatment and 30-day mortality for all episodes of L. monocytogenes bacteraemia and/or meningitis were collected by retrospective medical record review in the North Denmark Region and the Capital Region of Denmark (17 hospitals) from 1997 to 2012. Risk factors for 30-day all-cause mortality were assessed by logistic regression. The study comprised 229 patients (median age: 71 years), 172 patients had bacteraemia, 24 patients had meningitis and 33 patients had both. Significant risk factors for 30-day mortality were septic shock (OR 3.0, 95% CI 1.4-6.4), altered mental state (OR 3.6, 95% CI 1.7-7.6) and inadequate empiric antibiotic therapy (OR 3.8, 95% CI 1.8-8.1). Cephalosporins accounted for 90% of inadequately treated cases. Adequate definitive antibiotic treatment was administered to 195 patients who survived the early period (benzylpenicillin 72, aminopenicillin 84, meropenem 28, sulfamethoxazole/trimethoprim 6, and piperacillin/tazobactam 5). Definitive antibiotic treatment with benzylpenicillin or aminopenicillin resulted in a lower 30-day mortality in an adjusted analysis compared with meropenem (OR 0.3; 95% CI 0.1-0.8). In conclusion, inadequate empiric antibiotic therapy and definitive therapy with meropenem were both associated with significantly higher 30-day mortality.

Utilization of blood cultures in Danish hospitals: a population-based descriptive analysis.

This national population-based study was conducted as part of the development of a national automated surveillance system for hospital-acquired bacteraemia and ascertains the utilization of blood cultures (BCs). A primary objective was to understand how local differences may affect interpretation of nationwide surveillance for bacteraemia. From the Danish Microbiology Database, we retrieved all BCs taken between 2010 and 2013 and linked these to admission data from the National Patient Registry. In total, 4 587 295 admissions were registered, and in 11%, at least one BC was taken. Almost 50% of BCs were taken at admission. The chance of having a BC taken declined over the next days but increased after 4 days of admission. Data linkage identified 876 290 days on which at least one BC was taken; 6.4% yielded positive results. Ten species, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Enterococcus faecium, Enterococcus faecalis, Pseudomonas aeruginosa, Candida albicans, Enterobacter cloacae and Klebsiella oxytoca, accounted for 74.7% of agents for this purpose classified as pathogenic. An increase in BCs and positive BCs was observed over time, particularly among older patients. BCs showed a seasonal pattern overall and for S. pneumoniae particularly. A predominance of male patients was seen for bacteraemias due to S. aureus, E. faecium and K. pneumoniae. Minor differences in BCs and positive BCs between departments of clinical microbiology underpin the rationale of a future automated surveillance for bacteraemia. The study also provides important knowledge for interpretation of surveillance of invasive infections more generally.

Comparison of detection speed and yield in BACTEC NR-860 and Roche BCB blood culture systems.

Detection speed and yield were compared between BACTEC NR-860 and Roche BCB blood culture systems. From a total of 1,550 paired blood cultures inoculated with the same volume of blood, 161 (10.4%) grew 180 organisms from 140 adult patients. Sixty-six percent of the isolates were clinically significant. The BACTEC system detected more clinically significant isolates than the BCB system, 91% vs 76% (p < 0.01), especially Enterobacteriaceae. In 39 paired blood cultures, 42 significant organisms were detected at different times in the two systems. The vast majority (93%) were detected first (on average 1 day faster) by the BACTEC system (p < 0.05), especially Escherichia coli and streptococci. Generally, detection times were shorter in the BACTEC system. Three fourths (76%) of all significant organisms were detected within the first incubation day as compared to less than half (42%) in the BCB system (p < 0.001). Generally, the agitated aerobic resin medium BACTEC 26 Plus had the fastest detection and highest yield in our study. The contamination rate, below 2% in both systems, was acceptable. The BACTEC NR-860 system with resin-containing media proved to be a reliable, sensitive and fast blood culture system, which deserves further investigation.

Comparison of detection speed and yield in agitated and non-agitated aerobic blood culture bottles.

The influence of agitation on detection speed and yield was evaluated in 7,033 paired, identical aerobic blood culture bottles (Media Department, Statens Seruminstitut, Copenhagen, Denmark). One bottle was agitated and the other was incubated stationary. Of a total of 943 organisms isolated in aerobic blood culture bottles, 74% were clinically significant. No difference in the total yield of significant organisms was observed between agitated and non-agitated bottles. In the evaluation of detection speed, only cultures where organisms were isolated from both bottles, but at different times, were included, to ensure that no other factors influenced the result. Staphylococci, Pseudomonas spp., and Candida spp. were detected significantly faster in agitated bottles, on average 0.5-1 day earlier (p < 0.05), and in the majority of the cases within the first incubation day. These species are frequently found and are important causes of severe generalized infections, especially in immunocompromised patients, where early detection is of great importance. The detection principle in agitated bottles in our system, darkening of blood, proved to be an easy, reliable, and fast method to detect positive aerobic blood cultures, which could probably lead to increased automation.

Should aerobic blood cultures be shaken intermittently or continuously?

Stationary incubation of aerobic blood cultures was compared with intermittent shaking in aerobic Vacutainer 2630 bottles with agar slants during the first 24 h, and was simultaneously compared with the continuously shaken aerobic Bactec 6A bottles as a reference system. Intermittent shaking did not significantly increase or decrease the seven days yield of the Vacutainer bottles as compared with the continuously agitated Bactec 6A bottles. When one of 604 paired Vacutainer bottles was agitated for eight h and the other incubated stationary, the speed of growth detection was significantly greater in the agitated bottle (p less than 0.001), but significantly less than with continuously agitated Bactec 6A bottles (p less than 0.001). Agitation for 14 h showed the same pattern of detection speed. These results suggest that it is desirable initially to agitate aerobic blood cultures either intermittently or continuously.

Contaminating coagulase-negative staphylococci isolated in a lysis-centrifugation (Isolator) blood culture system. Application of different epidemiological markers for deduction of mode of contamination.

The lysis-centrifugation blood culture system, Isolator, is a promising system with respect to detection of many significant microorganisms, e.g. Staphylococcus aureus and Enterobacteriaceae, as compared with conventional systems. A drawback of the Isolator system is a disturbingly high rate of clinically insignificant, supposedly contaminating coagulase-negative staphylococci, which leads to considerable waste of time and materials in the laboratory. Several sources of these isolates have been proposed (viz. the patient, the ward environment, the laboratory handling, and the plate media). The aim of this study was to pinpoint the origin of these clinically doubtful coagulase-negative staphylococci, using different epidemiological markers, such as species identification, antibiotic susceptibility patterns, phage-types, and plasmid profiles. Plasmid profile analysis proved to be more discriminating than the other techniques and made it possible to conclude that the laboratory handling of the Isolator system was a major source of coagulase-negative staphylococci in this system.

Comparison between Bactec Nr. 660 and a conventional 12-tube blood culture system.

The detection power of the automated blood culture system Bactec NR 660, based on infrared detection of carbon dioxide in an agitated aerobic medium and a non-agitated anaerobic medium, was compared with that of our conventional 12-tube blood culture system. Of 1685 paired blood cultures, 258 (15.3%) were positive in one or both systems. Clinically relevant isolates were found in 11.5%. The dominating species were Escherichia coli(41%), followed by Staphylococcus aureus(14%) and Klebsiella spp.(8%). The Bactec system detected 178 (10.6%) and the 12-tube system 157 (9.3%) clinically relevant microorganisms after seven days' incubation. Significantly more clinically relevant isolates were detected by the Bactec system alone as compared with the conventional system alone (40 versus 19, p less than 0.01). The detection time was significantly shorter in the Bactec system for all isolates and for E. coli and S. aureus separately (p less than 0.01). 1.8% of the isolates in the Bactec system and 2.1% in the 12-tube system were considered clinically non-relevant contaminants.

A rat model of non-lethal bacterial infection.

The purpose of the study was to develop a small animal model of intraperitoneal infection without mortality and with a catabolic response to the infection, viz., to mimic the clinical situation in man. Intraperitoneal infection was induced in female Wistar rats by deposition of a gelatin capsule containing a mixture of Escherichia coli and Bacteroides fragilis and adjuvant substances. Seven groups of animals were infected with different bacterial inocula (0.2-4.3 x 10(6) CFU) to establish reproducible and dose-dependent changes in mortality, body weight in relation to food intake, blood cultures, peripheral blood leukocyte counts, and abscess formation on autopsy. No mortality was observed in animals with an inoculum below 2.2 x 10(6) CFU in spite of positive blood cultures. Initial weight loss was followed by weight gain in all animals except the group infected with the low inoculum (0.2 x 10(6) CFU). This group had no mortality, was in a catabolic state for three days, indicated by weight loss in spite of nearly normal food intake, and the infectious state was supported by intraperitoneal dissemination of small abscesses. The low-grade character of the infection was reflected by changes in peripheral blood lymphocyte and neutrophil granulocyte concentrations. In conclusion, this study presents a small animal model with a reproducible dose response to the bacterial challenge, allowing prolonged studies of metabolic changes following infection.

In vitro susceptibility of 124 Xanthomonas maltophilia (Stenotrophomonas maltophilia) isolates: comparison of the agar dilution method with the E-test and two agar diffusion methods.

The in vitro susceptibility of 124 Xanthomonas maltophilia isolates was tested by four methods: Agar dilution (reference method), E-test, a disk diffusion and a tablet diffusion method. Trimethoprim-sulfamethoxazole had the highest activity against X. maltophilia, followed by a combination of aztreonam-clavulanic acid at different ratios, the ratio 1:1 being the most active with a susceptibility rate of 85% as compared to 2% for aztreonam alone. Addition of the beta-lactamase inhibitor tazobactam to piperacillin enhanced the rate of susceptible isolates from 31% to 53%, Relatively few isolates were susceptible to ciprofloxacin (27%) and gentamicin (9%). Generally, the disk diffusion method had a considerably higher frequency of "very major" discrepancies when compared with the agar dilution method than with the other methods. The susceptibility of X. maltophilia to trimethoprim-sulfamethoxazole and ciprofloxacin could reliably be determined by all the diffusion methods tested, but otherwise the agar dilution method is to be preferred. A standardized and reliable diffusion method for susceptibility testing of X. maltophilia remains to be found. Trimethoprim-sulfamethoxazole must be considered the drug of choice in the treatment of severe X. maltophilia infections. The combination aztreonam-clavulanic acid is promising, but must be proved in a clinical setting.

Comparative analysis of two blood culture systems (Isolator and a 12-tube system) by cumulative differences in detection power at different times during incubation.

A lysis-centrifugation blood culture system (Isolator) and a conventional system (4 tubes of nutrient broth, 4 tubes of semisolid agar, and 4 tubes of thioglycollate agar) were compared after different lengths of incubation by cumulative scoring of differences in detection power. After the first half day of incubation, the Isolator system was already significantly faster in detecting isolates of clinical significance (15 vs. 4, P = 0.02). Maximum difference in first or only detection system was seen after two days of incubation and was based on an overall superior detection of Staphylococcus aureus (11 vs. 0, P = 0.001), and an earlier detection of Enterobacteriaceae (30 vs. 13, P = 0.01) in the Isolator system. On the contrary, the detection of Streptococcus pneumoniae was significantly inferior in the Isolator system (0 vs. 10, P = 0.002). The earlier finding of clinically significant microorganisms in the Isolator system certainly contributes to good patient-care. A drawback of the Isolator system was the finding of clinically insignificant coagulase-negative staphylococci in 11%, compared with 1% in the conventional system. This led to a considerable waste of time and materials in the laboratory. The comparison of the two blood culture systems, based on statistical analysis of cumulative differences in detection power, expressed as the earliest or only findings, gives the optimal information, and is in our opinion the clinically most relevant comparison.

Hypergonadotropinemia not associated to ovarian failure and induced by factors interfering in radioimmunoassay.

Unexpectedly high LH and FSH serum levels, measured by conventional RIA methods employing a rabbit antibody, were observed in eight women 18 to 34 years of age who came to our observation for acne and/or hirsutism and with no sign of premature ovarian failure. Reinvestigation of patient histories revealed that all of them had previously received multiple injections of a multimicrobial vaccine containing rabbit proteins. Luteinizing hormone and FSH were remeasured by IRMA and ELISA. These techniques revealed that serum levels of both gonadotropins were within the normal range in all subjects. We believe that falsely elevated gonadotropin levels were induced by the presence of heterophilic antibodies against rabbit serum interfering in the conventional RIA.