scholarly journals Pemphigus Foliaceous in a Dog - Clinical and Laboratorial Assessment

2020 ◽  
Vol 48 ◽  
Author(s):  
Virgínia Pereira Monteiro ◽  
Alexandre Tavares Camelo Oliveira ◽  
Tiago Cunha Ferreira
Keyword(s):  
Side Effects ◽  
Autoimmune Diseases ◽  
Inflammatory Process ◽  
Leukocyte Count ◽  
Neutrophil To Lymphocyte Ratio ◽  
Total Leukocyte Count ◽  
High Dose ◽  
Lymphocyte Ratio ◽  
Days Of Therapy

Background: The pemphigus complex is defined as a group of blistering autoimmune diseases that affects skin and mucous membrane. Pemphigus foliaceous is the most common disease in this group, being characterized by the production of autoantibodies against keratinocyte adhesion molecules. The treatment is based on the use of immunosuppressive drugs and requires constant monitoring to assess inflammatory control as well as side effects of therapy. Based on that, the aim of this study was to report the clinical and laboratorial follow-up of a canine with pemphigus foliaceous.Case: An 11-year-old male neutered mongrel dog, weighing 9.8 kg, was presented with a main complaint related to disseminated pruritus and lesions in face, trunk and limbs. Dermatological examination revealed meliceric crusts, epidermal collars and diffuse pustules in inguinal, abdominal, face, limbs, ears and thoraco-lumbar regions. Cytological examination was performed, revealing inflammatory and acantholytic cells and absence of bacterial cells. Biopsy procedure revealed subcorneal pustule with presence of epithelial acantholytic cells and neutrophils, compatible with canine pemphigus foliaceous. Hemoto-biochemical analysis revealed a leukocytosis due to increased neutrophil count. Systemic treatment with high dose of prednisolone (2.0 mg/kg) and azathioprine (2.5 mg/kg) was proposed, while topical therapy with a 3% chlorhexidine shampoo was used to prevent secondary bacterial infections. The patient improved the dermatological clinical signs, being possible to observe a reduction of systemic and tissue inflammatory process. After 90 days of therapy, there was a partial loss of hair body coverage, associated with follicular lesions, and after 180 days of therapy it was possible to notice a new hair mantle, without visible areas of inflammation.Discussion: The described clinical case demonstrates the clinical and laboratorial follow-up of a patient with naturally occurring canine pemphigus foliaceus. The main clinical characteristic of this disease is the formation of generalized pustular lesions, affecting regions such as the head, ear pinnae and limbs, which induced the diagnostic suspicion in the reported patient, in addition to the clinical history associated with complementary exams. In tissue evaluation, a pyogranulomatous inflammatory process was observed, with a marked presence of neutrophils and macrophages, which migrate from the dermis towards the epidermis. In systemic leukocyte analysis, an increase in the total leukocyte count was observed, due to the increase in circulating neutrophils. The therapy was based in use of a high dose of prednisolone associated with azathioprine. The following hemato-biochemical evaluations revealed a gradual reduction of systemic inflammatory process. Attention is drawn to neutrophil to lymphocyte ratio, which is a low-cost biomarker and less sensitive to pathophysiological changes when compared to individual leukocyte count. This parameter has been gaining visibility as a potential method of monitoring chronic inflammatory diseases. In veterinary medicine, its use is limited, with no reports related to canine pemphigus foliaceous in Brazil. After clinical and hematological improvement, prednisolone dose was slowly reduced, in order to avoid side effects. After clinical improvement, only azathioprine was maintained, in order to prevent critical flares. This report provides a clinical and laboratorial follow-up of a canine with pemphigus foliaceous, as well as it is the first one to describe the use of neutrophil to lymphocyte ratio to monitor therapeutic progression. New studies and reports involving this biomarker in autoimmune diseases monitoring are encouraged.

scholarly journals Mupirocin Pemphigus-Like Drug Reaction in a Dog

2019 ◽  
Vol 47 ◽  
Author(s):  
Tiago Cunha Ferreira ◽  
Rodrigo Fonseca De Medeiros Guedes ◽  
Belise Maria Oliveira Bezerra ◽  
Diana Célia Sousa Nunes-Pinheiro
Keyword(s):  
Side Effects ◽  
Autoimmune Diseases ◽  
Clinical Signs ◽  
Inguinal Region ◽  
Pemphigus Foliaceus ◽  
High Dose ◽  
Azathioprine Therapy ◽  
Dermatological Examination ◽  
Days Of Therapy ◽  
Triggering Factor

Background: Pharmacodermia is defined as adverse reaction in skin, mucosa and appendages, which generates morpho-functional alterations in cutaneous barrier, inducing autoimmune diseases, such as pemphigus foliaceous, which is known as the most common autoimmune skin disease in dogs. This disease involves autoantibodies against desmoglein and desmocolin molecules, being induced by the use of certain drugs. Mupirocin (pseudomonic acid A) is a broad-spectrum antibiotic with bacteriostatic activity, being effective against Gram-positive pathogens and used to control superficial bacterial folliculitis. Based on that, the aim of this study was to report a pemphigus-like lesions after topical use of mupirocin in dog.Case: An 1-year-old, uncastrated male, Poodle dog, weighing 13.8 kg was treated in a private clinic in Fortaleza. The main complaint was related to pruritus in abdominal and inguinal region, in addition of legs licking. Dermatological examination revealed melanic crusts, epidermal collars and diffuse pustules in inguinal, abdominal, perianal and thoraco-lumbar regions. The therapy was based on topical use of Mupirocin in form of 0.2% aquous spray. After drug administration, the animal presented urticaria, diffuse epidermal collars, papulo-crusted and pustular lesions, which were more evident in abdominal and inguinal region. Nasal erythema, binocular blepharitis, apathy and fever were also observed. Cytological examination and bacterial culture were performed, revealing inflammatory and acantholytic cells and no bacterial growth. Biopsy procedure revealed subcorneal pustule with presence of epithelial acantholytic cells and neutrophils, compatible with canine pemphigus foliaceous. The topical treatment of ocular lesions with 0.1% Tacrolimus associated with systemic treatment with high dose of prednisolone (1.2 mg kg-1). The patient improved the dermatological clinical signs, however, some side effects have already become evident, such as the presence of telangiectasia, polyuria, polyphagia and polydipsia. Heterodox therapy based on the use of azathioprine (2 mg kg-1) was chosen in order to reduce corticoid dose. After 3 days of therapy, blood material was collected for hepatic evaluation, detecting hepatotoxicity. From the results, azathioprine therapy was suspended, and only high-dose corticosteroid therapy (1.5 mg kg-1) was maintained. The patient presented a considerable improvement in the lesion after 10 days of treatment.Discussion: There have been reports that pharmacodermic reactions may be associated with the development of autoimmune diseases, such as pemphigus foliaceus and vulgaris. In some cases, the lesions regress after drug discontination. In others, the medication acts as a triggering factor, activating the genetic predisposition of patient, which develops the pathology even after therapy interruption. The drug related pemphigus-foliaceous is a well-recognized disease in humans, however this disease is limited to sporadic cases in dogs. The therapy was based in use of a high dose of prednisolone, which caused some side effects. Therefore, a heterodox therapy was chosen in order to reduce the corticoid dosage. At the first hemato-biochemical evaluation, the patient already presented significant alterations, being requested to suspend the prescribed treatment, although the owners already reported improvement of the dermatological lesions. Due to this, a higher dose of prednisolone was chosen, obtaining the best response among the therapies used since the beginning of the treatment. After clinical improvement, the gradual reduction of steroidal therapy was started in order to avoid side effects related to suppression of the hypothalamic-pituitary-adrenal axis. This report provides evidences of Mupirocin as a potential triggering factor of pemphigus-like lesions in dogs.

scholarly journals Polyglandular Autoimmune Syndrome Triggered after CTLA-4 and PD-1L Immunotherapy Treatment

Reports ◽  
2021 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Juan Luis Fernández-Morera ◽  
Alfredo Renilla González ◽  
Carmen Elena Calvo Rodríguez ◽  
Judit Romano-García
Keyword(s):  
Immune Response ◽  
Side Effects ◽  
Autoimmune Diseases ◽  
Autoimmune Diabetes ◽  
Hashimoto Thyroiditis ◽  
Polyglandular Autoimmune Syndrome ◽  
Autoimmune Syndrome ◽  
Previous Diagnosis ◽  
Optimal Approach

Background: CTLA-4 and PD-1L are novel immune checkpoint targets for cancer treatment with specific side effects such as autoimmune diseases. Less frequently, the presence of several autoimmune diseases in the same patient has been described. In this communication, we illustrate the case of a 45-year-old patient with a previous diagnosis of advanced cancer that, after starting treatment with this immunotherapy, developed in the following months autoimmune diabetes, lymphocytic hypophysitis, and a Hashimoto thyroiditis in an abrupt and intense manner that would correspond to an autoimmune polyglandular disease. Discussion: The activation of autoimmunity and associated diseases is increasing in parallel with augmented indication of these immunotherapeutic treatments in cancer patients. A closer follow-up of these patients could be necessary for an optimal approach to this type of pathology. Conclusions: Different autoimmune diseases can converge in the same patient when immunotherapy for cancer is indicated to boost immune response against tumor, caused by altering immune tolerance.

scholarly journals Association of Derived Neutrophil-To-Lymphocyte Ratio With Prognosis of Coronary Heart Disease After PCI

2021 ◽  
Vol 8 ◽  
Author(s):  
Gang-Qiong Liu ◽  
Wen-Jing Zhang ◽  
Jia-Hong Shangguan ◽  
Xiao-Dan Zhu ◽  
Wei Wang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Neutrophil To Lymphocyte Ratio ◽  
Major Adverse Cardiovascular Events ◽  
Lymphocyte Ratio ◽  
Coronary Syndrome ◽  
The Third

Aims: The present study aimed to investigate the prognostic role of derived neutrophil-to-lymphocyte ratio (dNLR) in patients with coronary heart disease (CHD) after PCI.Methods: A total of 3,561 post-PCI patients with CHD were retrospectively enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The patients (3,462) were divided into three groups according to dNLR tertiles: the first tertile (dNLR < 1.36; n = 1,139), second tertile (1.36 ≥ dNLR < 1.96; n = 1,166), and third tertile(dNLR ≥ 1.96; n = 1,157). The mean follow-up time was 37.59 ± 22.24 months. The primary endpoint was defined as mortality (including all-cause death and cardiac death), and the secondary endpoint was major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs).Results: There were 2,644 patients with acute coronary syndrome (ACS) and 838 patients with chronic coronary syndrome (CCS) in the present study. In the total population, the all-cause mortality (ACM) and cardiac mortality (CM) incidence was significantly higher in the third tertile than in the first tertile [hazard risk (HR) = 1.8 (95% CI: 1.2–2.8), p = 0.006 and HR = 2.1 (95% CI: 1.23–3.8), p = 0.009, respectively]. Multivariate Cox regression analyses suggested that compared with the patients in the first tertile than those in the third tertile, the risk of ACM was increased 1.763 times (HR = 1.763, 95% CI: 1.133–2.743, p = 0.012), and the risk of CM was increased 1.763 times (HR = 1.961, 95% CI: 1.083–3.550, p = 0.026) in the higher dNLR group during the long-term follow-up. In both ACS patients and CCS patients, there were significant differences among the three groups in the incidence of ACM in univariate analysis. We also found that the incidence of CM was significantly different among the three groups in CCS patients in both univariate analysis (HR = 3.541, 95% CI: 1.154–10.863, p = 0.027) and multivariate analysis (HR = 3.136, 95% CI: 1.015–9.690, p = 0.047).Conclusion: The present study suggested that dNLR is an independent and novel predictor of mortality in CHD patients who underwent PCI.

Prediction of renal cortical defect and scar using neutrophil-to-lymphocyte ratio in children with febrile urinary tract infection

2017 ◽  
Vol 56 (03) ◽  
pp. 109-114 ◽  
Author(s):  
Jeong Won Lee ◽  
Joon Soo Park ◽  
Kyeong Bae Park ◽  
Gyeong Hee Yoo ◽  
Seung Soo Kim ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Neutrophil To Lymphocyte Ratio ◽  
Febrile Urinary Tract Infection ◽  
Lymphocyte Ratio ◽  
Cortical Defect ◽  
Febrile Uti ◽  
Dmsa Scan

SummaryAim: This study is aimed to evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) for cortical defect on initial and follow-up Tc-99m dimercaptosuccinic acid (DMSA) scan in children with the first febrile urinary tract infection (UTI). Methods: We retrospectively enrolled 179 children with the first febrile UTI who underwent DMSA scan and laboratory tests. In patients with abnormal DMSA scan findings, follow-up DMSA scan was performed at least 6 months after the initial scan. All DMSA scans were classified as negative and positive cortical defects. Multiple logistic regression analyses were performed to identify the risk factors for cortical defect on initial and follow-up DMSA scan. Results: Cortical defects on initial DMSA scan were noted in 133 patients. Vesicoureteral reflux (VUR), white blood cell count, absolute neutrophil count, NLR, and serum C-reactive protein level were independent predictive factors for positive cortical defect on initial DMSA scan (p < 0.050). On follow-up DMSA scan, 24 of the 133 patients showed persistent cortical defects, and only VUR was significantly associated with persistent cortical defect (p = 0.002). In 84 patients who showed cortical defect on initial scan and absence of VUR, only NLR was significantly associated with persistent cortical defect on follow-up scan (p = 0.025). Conclusion: NLR was significantly associated with persistent cortical defect on follow-up DMSA scan in patients without VUR, as well as positive cortical defect on initial scan.

Activated and Expanded T Cells for Potential Therapy of Patients with Autoimmune Diseases.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3854-3854
Author(s):  
Alice Long ◽  
Mark Bonyhadi ◽  
Christophe Ferrand ◽  
Mark Frohlich ◽  
Ronald J. Berenson
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Side Effects ◽  
Autoimmune Diseases ◽  
Current Therapy ◽  
High Dose ◽  
Autoreactive T Cells ◽  
Repertoire Analysis ◽  
Tcr Repertoire

Abstract Autoreactive T cells have been implicated as central players in many autoimmune diseases. Current therapy for autoimmune diseases involves chronic immunosuppression, which increases the risk of infection and cancer, and is associated with other side effects. Recently, high-dose chemotherapy combined with stem cell transplantation has been used, but is often associated with severe toxicities. To avoid the side effects associated with these therapies, we are developing an alternative therapeutic approach in which patients are treated with relatively non-toxic therapy to reduce T cell numbers, and then administered healthy T cells to restore the immune system. Most autoimmune patients have oligoclonal populations of T cells as measured by T cell receptor (TCR) repertoire analysis. These may represent autoreactive T cells which contribute to TCR repertoire skewing. Clinical studies have shown a positive correlation between post-therapy TCR repertoire normalization and remission of autoimmune diseases. We have developed the Xcellerate™ Technology for the ex vivo activation and expansion of T cells. To expand T cells, peripheral blood mononuclear cells (PBMCs) are cultured with microscopic paramagnetic beads conjugated with anti-CD3 and anti-CD28 mAbs (Xcyte™Dynabeads®). T cells manufactured using this or a similar technology have been administered to patients with cancer and HIV in several clinical trials. In these studies, we and others have shown that the Xcellerate Technology can normalize skewed TCR repertoires in these patient populations. In the present study, we evaluated the use of the Xcellerate Technology to grow T cells from patients with autoimmune diseases such as rheumatoid arthritis, scleroderma, Crohn’s disease and systemic lupus erythematosus. We collected data on cytokine secretion, activation marker expression, cell expansion and TCR repertoire. T cells expanded an average of 1,325 fold (±1,592; range=16–6,532; n=35 patients), with nearly all cultures displaying marked CD25 and CD154 upregulation, and secretion of high levels of IFNγ and GM-CSF. Similar to results observed in cancer patients, TCR repertoire analysis showed that the Xcellerate Technology can normalize the skewed repertoires observed in autoimmune patients. Out of 12 PBMCs examined by spectratype analysis, one showed no TCR Vβ skewing prior to expansion, whereas the remaining 11 tissues displayed varying degrees of skewedness. After expansion, repertoire skewedness was decreased for all 11 samples. Repertoire normalization was dependent upon high-levels of TCR/CD28 engagement, which was achieved by initiating cultures using high bead to T cell ratios (Figure 1). Neither type of autoimmune disease, disease severity nor patient treatment (including: steroids, melphalan, infliximab, rapamycin, etc.) at the time of blood collection had an adverse effect on the ability to expand the patients’ T cells. Based on these results, the Xcellerate Technology may prove useful for generating healthy T cells from patients with autoimmune diseases which could then be used to restore the immune system following lymphoablative therapy. Studies are underway to further evaluate this approach. Figure Figure

Autologous Hematopoietic Stem Cell Transplantation In Neuromyelitis Optica: A Retrospective Study Of The EBMT Autoimmune Diseases Working Party In Collaboration With The University Of Sao Paulo, Ribeirao Preto, Brazil

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2125-2125
Author(s):  
Raffaella Greco ◽  
Attilio Bondanza ◽  
Manuela Badoglio ◽  
Myriam Labopin ◽  
Maria Carolina Oliveira ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Autoimmune Diseases ◽  
Working Party ◽  
High Dose ◽  
Free Survival ◽  
Disease Response

Abstract Background Neuromyelitis optica (NMO) is an inflammatory and demyelinating disorder of the central nervous system. Recently NMO has been recognized as an autoimmune astrocytopathy, distinct from multiple sclerosis and hallmarked by pathogenic anti-aquaporin 4 (AQP4) antibodies (Kim et al, Mult Scler, 2013). Currently NMO carries a poorer prognosis than multiple sclerosis (MS) and its response to various immunosuppressive treatments remains largely unsatisfactory. Use of Autologous stem cell transplantation (ASCT) has been reported worldwide as a tool for inducing prolonged restoration of self-tolerance in MS and other severe autoimmune diseases (AD), refractory to conventional treatments. In this context, NMO treatment resistant cases were considered for ASCT on a ‘Clinical Option’ basis, according to EBMT guidelines (Snowden et al, Bone Marrow Transplant, 2012). Only 2 isolated NMO cases with contradictory results (Matiello et al, Arch Neurol, 2011; Peng et al, Neurologist, 2010) and a Chinese report of 21 opticospinal multiple sclerosis patients treated by ASCT (Xu et al, Ann Hematol, 2011) are reported in the literature. Therefore, the EBMT Autoimmune Diseases Working Party (ADWP) conducted a survey to address NMO disease response following ASCT. Methods This retrospective study followed the EBMT study guidelines. All centers were invited to participate. Sixteen patients with aggressive forms of NMO refractory to standard treatments treated by ASCT between 2001 and 2011 had been reported to the EBMT registry. For each case, a specific questionnaire was sent to complete information by referring haematologist and neurologist about NMO, ASCT and outcome including disease response, relapse and progression. Results are reported as median. Results Patients (13 females and 3 males) had a median age of 37 years at transplant. Previous treatments had included high-dose steroids (12/16), immunoglobulins (5/16), iv cyclophosphamide (Cy, in 8/16), rituximab (5/16), mitoxantrone (2/16), plasma exchanges (8/16), azathioprine (5/16) and methotrexate (1/16). Median time between NMO diagnosis and transplant was 24 months. Before ASCT, the median EDSS (the Kurtzke Expanded Disability Status Scale) was of 6.5, 10/16 patients were positive for AQP4 antibodies and 11/16 had active lesions on magnetic resonance imaging (MRI). Peripheral blood stem cells mobilization, high-dose alkylating agent such as Cy (14/16) or monoclonal antibodies as Rituximab (2/16), followed by granulocyte colony stimulating factor (G-CSF), was successfully achieved in all cases (16/16). The conditioning regimen consisted of BEAM plus anti-thymocyte globulin (9/16) or Thiotepa-Cy (3/16) or Cy and anti-thymocyte globulin (4/16). Hematopoietic recovery was documented in all patients within 10 days (range 3-25) after ASCT, both for neutrophils and platelets, with a median number of 4 red blood cells and 5 platelet units transfusions. Infectious complications required specific treatment in 9 patients (6 febrile neutropenia, 5 CMV and 2 VZV reactivations, 1 aspergillosis). All patients responded initially. Relapse, necessitating further treatments, occurred in 13/16 at a median of 7 months after ASCT, presenting a median EDSS of 7 (range 3-8.5) and a worsening of MRI (11 cases). NMO progression was observed in 9/16 patients at a median of 10 months after ASCT. In the eight patients evaluable for AQP4 antibodies in the follow-up phase, the pathogenic autoantibodies remained positive after ASCT. Disease-free survival at 3 and 5 years were 31% and 10%, respectively, while progression-free survival at 3 and 5 years were 48%. No secondary malignancy was documented. All patients, but one patient who died from disease progression, are alive at a median follow up of 47 months after ASCT. Conclusions This EBMT retrospective study further demonstrates the potential of ASCT to reduce the highly inflammatory picture typical of NMO, at least in the short term, together with a low incidence of toxicities. Despite transient response after ASCT in the majority of cases, NMO relapsed at later time points underlying the need to investigate maintenance strategies to improve disease outcome in the long term after ASCT. Disclosures: No relevant conflicts of interest to declare.

Combining prognostic value of nodal ratio and neutrophil to lymphocyte ratio in completely resected gastric cancer with D2 lymph node dissection.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Andres Guevara ◽  
Daniel Enriquez ◽  
Patricia Elizabeth Rioja ◽  
Christian Pacheco ◽  
Victor Castro ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Neutrophil To Lymphocyte Ratio ◽  
Node Dissection ◽  
Early Disease ◽  
D2 Lymph Node Dissection ◽  
Lymphocyte Ratio ◽  
Nodal Ratio

e15565 Background: Outcomes in gastric cancer (GC) are still dismal even with complete D2 resection surgery and chemotherapy (CT), therefore identification of prognostic factors is critical to stratify patients at risk of recurrence or death. Nodal ratio (NR) has been recognized as a valuable prognostic factor and neutrophil to lymphocyte ratio (NLR) as systemic inflammation biomarker in some neoplasms. We evaluate overall survival (OS) combining NR and NLR among completely resected GC patients with D2 lymph node dissection in a Peruvian population. Methods: We reviewed retrospectively 791 medical records from GC pts with complete radical D2 resection between 2008 and 2012 at Instituto Nacional de Enfermedades Neoplasicas. We grouped according NR in < 0.2(Low), 0.2-0.5(Intermediate) and > 0.5(High), and NLR with cut-off < 3 and ≥3. We evaluated overall survival combining NR and NLR, also univariate and multivariate cox analysis were performed. OS was based on national registry and cannot evaluate DFS as long most patients return to their primary hospitals to follow-up. Results: Mean age was 60y [rank: 19-89]. Most frequent characteristics were distal localization (52.4%), intestinal subtype (52.6%) and poor differentiated histology (53%). From 791 patients, 156, 194 and 441 were diagnosed at I, II and III CS, respectively. Most patients had nodal involvement (66.8%), 21% and 28.4% received RT and CT, respectively. NLR < 3 was associated to early disease (p < 0.05). In nodal ratio groups, 68.9% had low, 23% intermediate and 8.1% high ratio, no differences were observed with NLR. At 5years median follow up, patients with NLR < 3 and low nodal ratio had better 5-year OS in this nodal group (71% vs 58% on NLR≥3; HR:0.75, 95%CI:0.49-0.94, p = 0.016]), and patients with intermediate and high nodal ratio had worse outcomes (25 and 15% 5year OS, respectively) without differences with NLR. Multivariate analysis showed higher nodal ratio had negative impact on OS. Conclusions: Neutrophil to lymphocyte ratio < 3 was associated to better OS in patients with low nodal ratio ( < 0.2), indeed this approach could be usefull to identify high risks patients with early disease in further studies.

Treatment of Serratia marcescens Meningitis with Prolonged Infusion of Meropenem

2007 ◽  
Vol 41 (6) ◽  
pp. 1077-1081 ◽  
Author(s):  
Anthony M Nicasio ◽  
Richard Quintiliani ◽  
C Andrew DeRyke ◽  
Joseph L Kuti ◽  
David P Nicolau
Keyword(s):  
Case Reports ◽  
High Dose ◽  
High Morbidity ◽  
Prolonged Infusion ◽  
Dosing Interval ◽  
Csf Penetration ◽  
Lumbar Drain ◽  
Days Of Therapy ◽  
The Central Nervous System

OBJECTIVE: To describe the use of and cerebral spinal fluid (CSF) penetration o a prolonged infusion meropenem regimen in a patient with Serratia marcescen meningitis. CASE SUMMARY: A 54-year-old female was diagnosed with S. marcescen meningitis associated with an epidural abscess 57 days after surgery for a herniated spinal disk. Meropenem 2000 mg every 8 hours was administered as a prolonged (3 h) infusion for the purpose of optimizing pharmacodynamic exposure Meropenem concentrations were measured from the patient's blood and CSF (via a lumbar drain). The prolonged infusion regimen resulted in concentrations in both serum and CSF above the meropenem minimum inhibitory concentration (MIC) o 0.047 μg/mL for 100% of the dosing interval. After 6 days of therapy, the patien showed no further signs of infection and was subsequently discharged to a rehabilitation facility. At follow-up, she had completed a 4 week course of the prolonged infused therapy without relapse or adverse events. DISCUSSION: Gram-negative infections of the central nervous system result in high morbidity and mortality. These infections are often difficult to treat because o poor antibiotic penetration coupled with increasing antibiotic resistance. Although there are 2 other case reports that describe the use of prolonged infusion o meropenem, our patient had a lumbar drain in place, thereby allowing us to collect multiple CSF samples and more accurately assess meropenem exposure at the site of infection. CSF penetration was 6.4% in this patient, resulting in 100% time above the MIC throughout the dosing interval. CONCLUSIONS: In this patient with meropenem-susceptible S. marcescensmenin gitis, the use of a high-dose prolonged infusion of meropenem resulted in adequate exposure at the site of infection and a successful clinical response.

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