Salvage of long-term central venous catheters during an outbreak of Pseudomonas putida and Stenotrophomonas maltophilia infections associated with contaminated heparin catheter-lock solution

objective. To describe the management of patients with long-term central venous catheters (CVCs) during an outbreak of infection due to Pseudomonas putida and Stenotrophomonas maltophilia associated with contaminated heparin catheter-lock solution. design. Descriptive study. setting. Private, 250-bed tertiary-care hospital. methods. In March 2003, we identified 2 febrile cancer patients with P. putida bacteremia. Over 2 days, 7 cases of bacteremia were identified; lots of syringes prefilled with heparin catheter-lock solution, supplied by a compounding pharmacy, were recalled and samples were cultured. More cases of bacteremia appeared during the following days, and any patient who had had a catheter lock infused with the suspect solution was asked to provide blood samples for culture, even if the patient was asymptomatic. Isolates that were recovered from culture were typed by pulsed-field gel electrophoresis. Antimicrobial salvage treatment of long-term CVCs was attempted. results. A total of 154 patients had had their catheter lock infused with solution from the lots that were suspected of being contaminated. Only 48 of these patients had CVCs. By day 7 of the outbreak, 18 of these patients had become symptomatic. Twenty-six of the remaining 30 asymptomatic patients then also provided blood samples for culture, 10 of whom developed fever shortly after samples were collected. Thirty-two patients were identified who had P. putida bacteremia; 9 also had infection due to S. maltophilia. Samples from 1 of the 3 lots of prefilled syringes in use at the time of the outbreak also grew P. putida on culture. Molecular typing identified 3 different clones of P. putida from patients and heparin catheter-lock solution, and 1 clone of S. maltophilia. A total of 27 patients received antimicrobial therapy regimens, some of which included decontamination of the catheter lock with anti- infective lock solution. Of 27 patients, 19 (70%) retained their long-term CVC during the 6-month follow-up period. conclusions. To our knowledge, this is one of the largest prospective experiences in the management of bloodstream infection associated with long-term CVCs. The infections were caused by gram-negative bacilli and were managed without catheter removal, with a high response rate. We emphasize the risks of using intravenous formulations of medications supplied by compounding pharmacies that produce large quantities of drugs.

The challenge of multidrug resistance: The treatment of gram-negative rod infections

Infections caused by multidrug-resistant gram-negative bacteria are an increasing problem worldwide. Treatment of these microorganisms is a challenge because resistance limits dramatically therapeutic options. In this review, we discuss data of in vitro susceptibility and clinical studies of possible agents for the management of these infections. Currently, published data are limited, and there are no randomized clinical trials involving the treatment of infections caused by multidrug-resistant gram-negative rods. For imipenem-resistant Acinetobacter spp., most studied options are polymyxins and sulbactam. No newer antimicrobials active against Pseudomonas aeruginosa are available or under investigation. Tigecycline presents a broad spectrum of activity in vitro but has been studied mainly as treatment of community-acquired infections, as has ertapenem. They are potential options against extended-spectrum P-lactamase-producing Enterobacteriaceae, and tigecycline may be useful in treating Acinetobacter infections.

Neuropharmacological basis of rTMS-induced analgesia: The role of endogenous opioids

We investigated the role of endogenous opioid systems in the analgesic effects induced by repetitive transcranial magnetic stimulation (rTMS). We compared the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after naloxone or placebo treatment, in a randomized, double-blind crossover design, in healthy volunteers. Three groups of 12 volunteers were selected at random and given active stimulation (frequency 10 Hz, at 80% motor threshold intensity, 1500 pulses per session) of the right M1, active stimulation of the right DLPFC, or sham stimulation, during two experimental sessions 2 weeks apart. Cold pain thresholds and the intensity of pain induced by a series of fixed-temperature cold stimuli (5, 10, and 15 degrees C) were used to evaluate the analgesic effects of rTMS. Measurements were made at the left thenar eminence, before and 1 hour after the intravenous injection of naloxone (bolus of 0.1 mg/kg followed by a continuous infusion of 0.1 mg/kg/h until the end of rTMS) or placebo (saline). Naloxone injection significantly decreased the analgesic effects of M1 stimulation, but did not change the effects of rTMS of the DLPFC or sham rTMS. This study demonstrates, for the first time, the involvement of endogenous opioid systems in rTMS-induced analgesia. The differential effects of naloxone on M1 and DLPFC stimulation suggest that the analgesic effects induced by the stimulation of these 2 cortical sites are mediated by different mechanisms. (C) 2010 Published by Elsevier B.V. on behalf of International Association for the Study of Pain.

CHOREA IN A CHILD WITH CHURG-STRAUSS SYNDROME

Introduction: Churg-Strauss syndrome (CSS) is a systemic granulomatous vasculitis rarely described in children, particularly associated with neurological involvement, exceptionally chorea. To our knowledge there are only 35 children and adolescent patients with CSS described in the literature. During a 25-year period 5283 patients were followed up at the Pediatric Rheumatology Unit of our University Hospital and only one (0.02%) presented CSS. Case report: A 7-year-old boy suffered from severe asthma, eosinophilia, history of allergy, recurrent non-fixed pulmonary infiltrates, several nodular lesions in both lungs and maxillary sinusitis. Transthoracic biopsy of the right lung revealed necrotizing extravascular eosinophilic infiltrates and the diagnosis of CSS was established. During the follow-up he had persistent vasculitis skin lesions and hemichorea. Despite the treatment with immunosuppressive drugs and intravenous immunoglobulin, he died because of pulmonary abscess and sepsis. Discussion: A rare case of CSS with chorea was reported, reinforcing the possibility of this disease in children with asthma, allergic rhinitis, hypereosinophilia and cutaneous vasculitis.

Neutropenia in antibody-deficient patients under IVIG replacement therapy

Patients with antibody deficiencies are more prone to develop acute neutropenic episodes even during immunoglobulin replacement. The aims of this study were to evaluate the presence of acute neutropenia in 42 patients with primary antibody immunodeficiencies, currently receiving intravenous immunoglobulin (IVIG), and to describe the clinical and laboratory findings during neutropenic episodes. Of all patients, 10 (23.8%) presented acute neutropenia (absolute neutrophil count < 1500 cells/mm(3)) during follow up (mean of 6.4 yr). The absolute neutrophil count ranged from 71 to 1488 cells/mm(3). Neutropenia was not clearly associated with antibiotic prophylactic therapy or immunoglobulin levels, while infections were associated with neutropenia in the majority of episodes. Most acute neutropenia episodes were mild or moderate, except in CVID patients who present more severe neutropenia. Although IVIG may have contributed to reducing the severity of neutropenia, it does not prevent its occurrence in all patients. In conclusion, primary immunodeficient patients, even submitted to IVIG replacement therapy, must be regularly evaluated for neutropenia in order to minimize the risk of infections and its appropriate approach.

Alterations in Cytokine Profile and Dendritic Cells Subsets in Peripheral Blood of Rheumatoid Arthritis Patients before and after Biologic Therapy

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic joint inflammation and continuous immune cell infiltration in the synovium. These changes are linked to inflammatory cytokine release, leading to eventual destruction of cartilage and bone. During the last decade new therapeutic modalities have improved the prognosis, with the introduction of novel biological response modifiers including anti-TNF alpha CTLA4Ig and, more recently, anti-IL6. In the present study we looked at the immunological effects of these three forms of therapy. Serum, obtained from patients with RA was analyzed for TNF alpha, IL6, IL10, IFN gamma, and VEGF, and in parallel, circulating plasmacytoid and myeloid dendritic cells (DC) were enumerated before and after three infusions of the respective biological treatments. After treatment with anti-IL6, we found a significant reduction of IL6 and TNF alpha levels and the percentage of both DC subsets decreased. Although the results did not reach statistical significance for anti-TNF alpha treatment, similar trends were observed. Meanwhile, CTLA4Ig therapy led to the reduction IFN gamma levels only. None of the treatments modified significantly VEGF or IL10 levels. These findings may explain why patients with RA improve more rapidly on IL-6 therapy than with the other two modalities.

PENILE AND SCROTUM SWELLING IN JUVENILE DERMATOMYOSITIS

Edema is a well-known feature of juvenile dermatomyositis (JDM). However, to our knowledge localized penile and scrotum swelling was not previously reported. During a 27-year period, 5,506 patients were followed up at the Pediatric Rheumatology Unit of our University Hospital and 157 patients (2.9%) had JDM. One of them (0.6%) had concomitant localized penile and scrotum swelling. He had severe disease activity since he was 7-year-old, manifested by diffuse cutaneous vasculitis, recurrent localized edema (limbs or face) and only one episode of generalized edema. At the age of 10, he presented edema of the genitalia associated with mild skin erythema. Penis, scrotum and testicular ultrasound as well as magnetic resonance imaging showed skin edema without testicular involvement. He was taking prednisone, methotrexate, cyclosporin, hydroxychloroquine and thalidomide. Improvement of skin rash, penile and scrotum swelling was noticed only with rituximab therapy. No adverse event was observed during anti-CD20 infusions and after six months of follow up. Penile and scrotum edema was a rare manifestation of JDM which improved with anti-CD20 monoclonal antibody treatment.

C4d staining in post-reperfusion renal biopsy is not useful for the early detection of antibody-mediated rejection when CDC crossmatching is negative

Background. Sensitized patients (pts) may develop acute antibody-mediated rejection (AMR) due to preformed donor-specific antibodies, undetected by pre-transplant complement-dependent cytotoxicity (CDC) crossmatch (XM). We hypothesized that C4d staining in 1-h post-reperfusion biopsies (1-h Bx) could detect early complement activation in the renal allograft due to preformed donor-specific antibodies. Methods. To test this hypothesis, renal transplants (n = 229) performed between June 2005 and December 2007 were entered into a prospective study of 1-h Bx and stained for C4d by immunofluorescence. Transplants were performed against a negative T-cell CDC-XM with the exception of three cases with a positive B-cell XM. Results. All 229 1-h Bx stained negative for C4d. Fourteen pts (6%) developed AMR. None of the 14 protocol 1-h Bx stained positive for C4d in peritubular capillaries (PTC). However, all indication biopsies-that diagnosed AMR-performed at a median of 8 days after transplantation stained for C4d in PTC. Conclusions. These data show that C4d staining in 1-h Bx is, in general, not useful for the early detection of AMR when CDC-XM is negative.

Anemia During Pregnancy after Silastic Ring Roux-en-Y Gastric Bypass: Influence of Time to Conception

Bariatric surgery before pregnancy may help prevent obesity-related gestational complications. However, maternal malnutrition is not without potential risks during pregnancy. The objective was to evaluate the influence of time to conception after silastic ring Roux-en-Y gastric bypass (SRYGB) on maternal anemia. Patients who underwent SRYGB for morbid obesity and who subsequently became pregnant were followed up at the prenatal. Thirty pregnancies occurred between July 2001 and September 2009. The patients were analyzed according to time to conception after bariatric surgery: 17 patients with time to conception < 4 years (48 months) and 13 patients with a parts per thousand yen4 years. First trimester hemoglobin levels were significantly lower in patients with time to conception a parts per thousand yen4 years (48 months) (median 9.6 g/dL, range 5.8-13.2 g/dL) than in patients with time to conception < 4 years (median 11.1 g/dL, range 9.8-13.6 g/dL; p = 0.047). The need for intravenous iron therapy or packed red cell transfusion was significantly more frequent among women who became pregnant a parts per thousand yen4 years after SRYGB compared to < 4 years (30.8% vs. 0%, p = 0.026). Pregnancy after 4 years of SRYGB is associated with maternal anemia and the need for more strict iron supplementation.

Description of Nosocomial Infection Prevention Practices by Anesthesiologists in a University Hospital

Kishi D; Videira RLR Description of Nosocomial Infection Prevention Practices by Anesthesiologists in a University Hospital. Background and objectives: Anesthesiologists play an important role in the prevention of nosocomial infections. In anesthetic practice, physiologic barriers are routinely breached, allowing patient contamination with microorganisms and the consequent development of infection. The lack of adhesion to recommended practices can facilitate transmission of microorganisms. It is important to describe prophylactic practices of anesthesia-related nosocomial infections performed by anesthesiologists. Methods: Structured questionnaires were distributed to be answered voluntarily and anonymously by anesthesiologists. Results: Among 112 anesthesiologists, 75% answered the questionnaire. Surgical mask is used by 95.2% of anesthesiologists, 96.3% wear gloves frequently, 98.9% wear sterile gloves for neuraxial block, 91.3% use sterile technique for central venous puncture, 95.1% wash their hands between cases, 91.6% try to maintain the endotracheal tube sterile, 96.3% discard the prefilled propofol syringe at the end of each anesthesia, 30% clean the vials before using it in the neuraxial blocks, and 19.8% clean the vials before intravenous use. Conclusions: Respondents showed good adhesion to practices of nosocomial infection prophylaxis and to improve them educational multidisciplinary campaigns are necessary.

Acute pancreatitis in juvenile systemic lupus erythematosus: a manifestation of macrophage activation syndrome?

Acute pancreatitis (AP) is a rare and life-threatening manifestation of juvenile systemic lupus erythematosus (JSLE). The objective of this study was to evaluate the prevalence and clinical features of AP in our JSLE population. AP was defined according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Of note, in the last 26 years, 5367 patients were followed up at our Pediatric Rheumatology Unit and 263 (4.9%) of them had JSLE diagnosis (ACR criteria). AP was observed in 4.2% (11/263) of JSLE patients. The median of age of the JSLE patients at AP diagnosis was 12.4 years (8.8-17.9). All of them had lupus disease activity at AP onset. Three patients were receiving corticosteroids before AP diagnosis. Interestingly, 10/11 JSLE patients fulfilled preliminary guidelines for macrophage activation syndrome, three of them with macrophage hemophagocytosis in bone marrow aspirate and hyperferritinemia. The hallmark of this syndrome is excessive activation and proliferation of T lymphocytes and macrophages with massive hypersecretion of proinflammatory cytokines and clinically it is characterized by the occurrence of unexplained fever, cytopenia and hyperferritinemia. AP treatment was mainly based on intravenous methylprednisolone. Four JSLE patients with AP died and two developed diabetes mellitus. In conclusion, AP was a rare and severe manifestation in active pediatric lupus. The association between AP and macrophage activation syndrome suggests that the pancreas could be a target organ of this syndrome and that pancreatic enzyme evaluation should also be carried out in all patients. Lupus (2010) 19, 1654 1658.

Special care dentistry: Midazolam conscious sedation for patients with neurological diseases

Aim Midazolam is used very often to control the anxiety of patients for dental treatment especially in patients with special needs. The objective of this study was to evaluate the efficiency of Midazolam in patients with neurological diseases referred for dental treatment. Study design Descriptive study Methods Forty consecutive patients with neurological disorders (encephalopathy, autism, and epilepsy) were referred to dental treatment, and 45 sedations were performed; all were sedated with Midazolam (intramuscular 0.2-0.3 mg/kg or intravenous 0.1mg/kg) and all were anesthetised with lidocaine 2% (0.5-2 mL). During the dental procedure, their behavior was analysed and classified into 3 categories: A (indifferent), 8 (reacted but allowed treatment), and C (did not allow treatment). Data were tabbed and statistically analysed. Results The final patients` classification was: A 22 (49%), 8 18 (40%) and C 5 (11%); the patients with encephalopathy had the best results of sedation according to the proposed classification (p<0.05). Conclusion Midazolam demonstrated to be effective in 89% of this sample for dental procedures in patients with neurological and behavioral disturbances, but it was less effective for patients with autism (p<0.05).

Multiple Clinical Presentations of Lymphoproliferative Disorders in Pediatric Liver Transplant Recipients: A Single-Center Experience

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation that has been linked to Epstein-Barr virus (EBV) infection. The aim of this article was to describe a single-center experience with the multiplicity of clinical presentations of PTLD. Among 350 liver transplantations performed in 303 children, 13 survivor children displayed a histological diagnosis of PTLD (13/242 survivors; 5.4%). The age at diagnosis ranged from 12 to 258 months (median, 47), and the time from transplantation ranged from 1 to 84 months (median, 13). Ten of these children (76.9%) were EBV-naive prior to transplantation. Fever was present in all cases. The clinical signs at presentation were anemia (92.3%), diarrhea and vomiting (69.2%), recurrent upper airway infections (38.4%), Waldeyer ring lymphoid tissue hypertrophy (23.0%), abdominal mass lesions (30.7%), massive cervical and mediastinal adenopathy (15.3%), or gastrointestinal and respiratory symptoms (30.7%). One child developed fulminant hepatic allograft failure secondary to graft involvement by PTLD. Polymorphic PTLD was diagnosed in 6 patients; 7 had the diagnosis of lymphoma. Treatment consisted of stopping immunosuppression as well as starting intravenous gancyclovir and anti-CD20 monoclonal antibody therapy. The mortality rate was 53.8%. The clinical presentation of PTLD varied from fever of unknown origin to fulminant hepatic failure. The other symptoms that may be linked to the diagnosis of PTLD are pancytopenia, tonsil and adenoid hypertrophy, cervical or mediastinal lymph node enlargement, as well as abdominal masses. Despite numerous advances, the optimal treatment approach for PTLD is not completely known and the mortality rate is still high.

Impact of Cytomegalovirus Infection in Lung Transplant Patients Under Universal Prophylaxis: Single-Center Experience in Brazil

Introduction. Cytomegalovirus (CMV) infection, a common complication in lung transplant (LT) patients, is associated with worse outcomes. Therefore, prophylaxis and surveillance with preemptive treatment is recommended. Objectives. Describe the epidemiology and impact on mortality of CMV infection in LT patients receiving CMV prophylaxis. Methods. Single-center retrospective cohort of LT recipients from August 2003 to March 2008. We excluded patients with survival or follow-up shorter than 30 days. We reviewed medical charts and all CMV pp65 antigen results. Results. Forty-seven patients met the inclusion criteria and 19 (40%) developed a CMV event: eight CMV infections, seven CMV syndromes, and 15 CMV diseases. The mean number of CMV events for each patient was 1.68 +/- 0.88. Twelve patients developed CMV events during prophylaxis (5/12 had CMV serology D+/R-). Forty-six of the 47 patients had at least one episode of acute rejection (mean 2.23 +/- 1.1). Median follow-up was 22 months (range = 3-50). There were seven deaths. Upon univariate analysis, CMV events were related to greater mortality (P = .04), especially if the patient experienced more than two events (P = .013) and if the first event occurred during the first 3 months after LT (P = .003). Nevertheless, a marginally significant relationship between CMV event during the first 3 months after LT and mortality was observed in the multivariate analysis (hazards ratio: 7.46; 95% confidence interval: 0.98-56.63; P = .052). Patients with CMV events more than 3 months post-LT showed the same survival as those who remained CMV-free. Conclusion. Prophylaxis and preemptive treatment are safe and effective; however, the patients who develop CMV events during prophylaxis experience a worse prognosis.

Prednisone monotherapy induced remission in a group of patients with membranous lupus nephritis

The treatment of membranous lupus nephritis (MLN) is still controversial in the literature. We conducted a retrospective analysis of patients in two medical centers of Sao Paulo-Brazil in order to evaluate the clinical response in patients submitted to either a regimen with prednisone alone or to a double immunosuppressive regimen (prednisone plus cyclophosphamide or prednisone plus azathioprine). Methods: MLN female patients were enrolled in this retrospective study conducted from February 1999 to June 2007. Data were collected from the patients` medical charts. Race distribution was similar in both groups: Caucasian (72.3%) and Afro-Latin-American (27.7%). The prednisone regimen consisted of 1 mg/kg/day for 8 weeks and tapering until 0.1 mg/kg/day (n = 29). The double immunosuppressive treatment consisted of the same doses of prednisone plus monthly intravenous cyclophosphamide or azathioprine for 6 months (n = 24). Criteria for remission (complete and partial) and renal function loss as well as flare criteria followed those used in the literature. Results: There was no difference between the prednisone group and the double immunosuppressive group regarding age (33.2 +/- 9.4 vs. 29.1 +/- 9.1 y), estimated GFR (76.5 +/- 26.6 vs. 74.1 +/- 39.6 ml/min/1.73 m(2)), serum albumin (2.8 +/- 0.7 vs. 2.6 +/- 0.3 g/dl), positive ANA (87.5 vs. 90.0%), positive anti-dsDNA (47.6 vs. 44.0%), renal SLEDAI indices (6.6 +/- 2.6 vs. 7.0 +/- 3.1), follow-up time (71 +/- 46 vs. 62 +/- 45 months), as well as proteinuria (3.1 +/- 1.9 vs. 4.8 +/- 2.4 g/day) and number of non-nephrotic patients (6 in the prednisone group vs. 3 in the double immunosuppressive group). The prednisone group presented higher C3 values (85.2 +/- 31.5 vs. 62.3 +/- 41.6 U/ml, p = 0.04). Clinical and laboratory characteristics at 6 months and at last follow-up did not reveal any differences between treatment regimens. Renal survival after an 8-year follow-up did not differ in both groups (prednisone group 86.2% vs. double immunosuppressive group 75%), and patients in both groups showed a high rate of renal flares (prednisone group 51.7% vs. double immunosuppressive group 62.5%). Univariate analysis showed that only patient age predicted flares (r = -0.048, p = 0.04). Borderline significance was obtained for proteinuria analysis (p = 0.07). Adverse effects did not differ between the groups. Conclusions: A regimen of corticosteroids in MLN induced a high remission rate after 6 months. Both treatment regimens showed a high flare rate and age was the only predictive parameter (r = -0.048, p = 0.04). Renal survival after 8 years did not differ between the groups.