Early Broad-spectrum Antibiotics Research Articles

Evaluating Antibiotic De-escalation for Autologous Stem Cell Transplant Patients With Febrile Neutropenia in a Real-World Clinical Setting

Febrile neutropenia (FN) is a complication in approximately 90% of autologous stem cell transplant (SCT) patients. Guidelines support early broad-spectrum antibiotics (BSA) to prevent morbidity and mortality. However, in patients who are clinically stable and deemed to have a fever of unknown origin, the optimal duration of BSA is unknown. Accumulating evidence suggests that de-escalation of BSA in select patients may decrease duration of BSA exposure without compromising clinical outcomes such as infection, recurrent fever, and readmission. With this, a de-escalation protocol was implemented at Vanderbilt University Medical Center (VUMC) to identify autologous SCT patients who may benefit from early de-escalation of BSA. The objectives of this study were to analyze the impact of early empiric antibiotic de-escalation on the duration of BSA as well as its impact on the incidence of recurrent fever and documented infection in autologous SCT patients. This was a single-center, retrospective study evaluating patients older than 18 years of age who underwent autologous SCT and experienced an episode of FN from January 2018 to December 2022 at VUMC (N = 195). The protocol was initiated on January 1, 2020, to de-escalate BSA back to prophylaxis in stable neutropenic patients determined to have a fever of unknown origin. The primary outcome was the number of BSA days within 30 days. Secondary clinical outcomes included recurrent fever, documented infection, readmission, 30-day mortality, and 90-day non-relapsed mortality (NRM). Outcomes were compared across pre- and post-protocol groups with a Wilcoxon rank sum test, Pearson chi-square test, or regression analysis as appropriate. The median BSA duration was 4.7 and 2.7 days in the pre- and post-protocol groups, respectively (p <0.001). Recurrent fever (14.2% vs. 16.0%, p = 0.726), documented infection (1.7% vs. 6.7%, p = 0.068), and readmission (13.3% vs. 22.7%, p = 0.091) within 30 days were not significantly different between the two groups. Neither 30-day mortality (0.8% vs. 1.3%, p = 0.736) nor 90-day NRM (0.8% vs. 1.3%, p = 0.736) differed. The implementation of an early de-escalation protocol for autologous SCT patients who develop FN was associated with a reduction in duration of BSA compared to the pre-protocol group without a significant difference in readmission, recurrent fevers, and documented infections. This study adds to existing evidence that early de-escalation of BSA in FN patients with a fever of unknown origin who are afebrile and clinically stable is safe and reduces unnecessary antibiotic use.

Sepsis Management in Southeast Asia: A Review and Clinical Experience.

Sepsis is a life-threatening condition that causes a global health burden associated with high mortality and morbidity. Often life-threatening, sepsis can be caused by bacteria, viruses, parasites or fungi. Sepsis management primarily focuses on source control and early broad-spectrum antibiotics, plus organ function support. Comprehensive changes in the way we manage sepsis patients include early identification, infective focus identification and immediate treatment with antimicrobial therapy, appropriate supportive care and hemodynamic optimization. Despite all efforts of clinical and experimental research over thirty years, the capacity to positively influence the outcome of the disease remains limited. This can be due to limited studies available on sepsis in developing countries, especially in Southeast Asia. This review summarizes the progress made in the diagnosis and time associated with sepsis, colistin resistance and chloramphenicol boon, antibiotic abuse, resource constraints and association of sepsis with COVID-19 in Southeast Asia. A personalized approach and innovative therapeutic alternatives such as CytoSorb® are highlighted as potential options for the treatment of patients with sepsis in Southeast Asia.

Best practice for the treatment of descending mediastinitis: A review of review articles and studies looking at cause, diagnosis, treatment and outcomes of head and neck descending necrotizing mediastinitis

Introduction: Descending necrotizing mediastinitis (DNM) is a rare but serious infection. The aim of this review is to highlight the common pathogens and risk factors associated with DNM as well as depicting both the medical and surgical treatments. Methods: A literature search of the Cochrane libraries and PubMed libraries for articles published between January 2000 and December 2020 reporting on DNM were reviewed. The key words used: descending necrotizing mediastinitis, odontogenic infection, cervical infection. 3 surgeons evaluated 40 abstracts. Only literature reviews and studies were included. Results: The total number of papers included were 14, 8 articles were reviews of the literature and 6 articles were original studies. Patient outcomes are better the earlier that the condition is diagnosed and treated. CT neck and thorax was the best imaging modality. Odontogenic with streptococcal species is most common cause and the most effective antibiotic sensitivity is a third-generation cephalosporin or clindamycin combined with metronidazole. An alternative is a penicillin with metronidazole. Prompt surgical management is required to effectively debride necrotic tissue. Airway management is an important consideration. Hyperbaric oxygen can be an useful adjunct to treatment. Conclusions: Early treatment of descending mediastinits is imperative for best outcome. Imaging of choice is a CT neck and thorax. Early broad-spectrum antibiotics and surgical intervention is key. Introduction: Descending necrotizing mediastinitis (DNM) is a rare but serious infection. The aim of this review is to highlight the common pathogens and risk factors associated with DNM as well as depicting both the medical and surgical treatments. Methods: A literature search of the Cochrane libraries and PubMed libraries for articles published between January 2000 and December 2020 reporting on DNM were reviewed. The key words used: descending necrotizing mediastinitis, odontogenic infection, cervical infection. 3 surgeons evaluated 40 abstracts. Only literature reviews and studies were included. Results: The total number of papers included were 14, 8 articles were reviews of the literature and 6 articles were original studies. Patient outcomes are better the earlier that the condition is diagnosed and treated. CT neck and thorax was the best imaging modality. Odontogenic with streptococcal species is most common cause and the most effective antibiotic sensitivity is a third-generation cephalosporin or clindamycin combined with metronidazole. An alternative is a penicillin with metronidazole. Prompt surgical management is required to effectively debride necrotic tissue. Airway management is an important consideration. Hyperbaric oxygen can be an useful adjunct to treatment. Conclusions: Early treatment of descending mediastinits is imperative for best outcome. Imaging of choice is a CT neck and thorax. Early broad-spectrum antibiotics and surgical intervention is key.

Tumor inflamatorio de pott. Descripción de un caso

RESUMEN Introducción y objetivo: El tumor inflamatorio de Pott se describe como una inflama-ción en la región frontal debido la formación de un absceso subperióstico y osteo-mielitis del hueso frontal; debido en la mayoría de las ocasiones, a una sinusitis fron-tal. Es más frecuente observarlo en adolescentes. El objetivo de nuestro estudio es presentar un diagnóstico un tanto olvidado y poco frecuente; así como su descrip-ción como entidad en la discusión de los artículos más relevantes de la literatura. Descripción: Presentamos el caso de un varón de 61 años con cefalea punzante a nivel supraciliar derecha, sin insuficiencia respiratoria nasal y con fibroscopia prácti-camente anodina. En la inspección se observa una inflamación, dolorosa a la palpa-ción, del tejido blando con una pequeña fistulización hacia la piel y salida de material purulento. En el TC de senos paranasales se observa una sinusitis crónica frontal derecha. Dicho seno presenta una solución de continuidad en su pared anterior que comunica las partes blandas. Se realiza Draf III del seno frontal derecho guiado con neuronavegador con abordaje combinado externo y vancomicina IV intrahospitalaria. Actualmente el paciente se encuentra asintomático sin clínica infecciosa. Discusión: el tumor inflamatorio de Pott es una complicación rara, pero potencialmente mortal de la sinusitis bacteriana, que consiste en un absceso subperióstico y osteomielitis del hueso frontal. Se diagnostica con tomografía computarizada con contraste o reso-nancia magnética y se trata con antibióticos de amplio espectro, así como interven-ción quirúrgica de forma precoz. Es necesario conocer la fisiopatología y manejo del cuadro; evitando así las posibles complicaciones intracraneales. Conclusiones: el diagnóstico precoz de esta entidad y el tratamiento antibiótico y endoscópico son esenciales para evitar el riesgo de progresión hacia complicaciones neurológicas graves subsidiarias de tratamientos quirúrgicos más agresivos.

Early Broad-Spectrum Antibiotics and Risk of Acute Graft-Versus-Host Disease in Children: An Analysis from the Center for International Blood and Marrow Transplantation Research (CIBMTR) and the Pediatric Health Information System (PHIS)

Background Variation in the gastrointestinal microbiota after hematopoietic cell transplantation (HCT) has been associated with acute graft-versus-host disease (aGVHD). The significant immunosuppression associated with HCT leads to frequent broad-spectrum antibiotic exposures that in turn drive host microbiota composition. We sought to explore the association of different antipseudomonal antibiotic classes, commonly administered as empiric therapy for neutropenic fever, with subsequent aGVHD-risk in a large, multicenter cohort of children undergoing HCT for acute leukemia. We hypothesized that antibiotic classes that retain broad anti-anaerobic activity would increase aGVHD due to the greater potential impact of these agents on the microbiota. Methods Children 1-21 years old who underwent first HCT for acute leukemia from 2004 to 2017 were identified in 2 databases: CIBMTR, an observational database with demographic, transplant and outcomes information, and PHIS, an administrative database with resource utilization data from freestanding children's hospitals. Patients were then merged based on date of birth, date of transplant, sex and disease. The outcome was grade 2-4 aGVHD by day +100. The primary exposures were 3 distinct classes of antibiotics commonly used for empiric therapy: (1) antipseudomonal cephalosporins, (2) antipseudomonal penicillins and (3) carbapenems. They were captured as days of therapy from conditioning start to day +7, and classified as no, low (1-3 days), or high (&amp;gt;3 days) exposure. Logistic regression was applied to evaluate the association between aGVHD and each exposure, controlling for exposure to the other two classes. For the subset of patients with data on date of GVHD onset, a time to event analysis was performed considering death without GVHD as a competing event. For both analyses, we constructed multivariable models that were informed by a directed acyclic graph and included covariates representing demographics, transplant characteristics and GVHD risk factors associated with both exposure and outcome. The adjusted models also included exposure to other antibiotics within the same window, captured as fluoroquinolones, intravenous vancomycin and other adjunctive antibiotics, with and without anti-anaerobic activity. Generalized estimating equations with robust variance estimates were employed to account for clustering at the hospital level. Results The assembled cohort included 2,501 patients at 35 hospitals. One-third of patients (36.6%) developed aGVHD, 4.4% died without GVHD and no patients were lost to follow-up. The proportion of patients exposed to at least 1 day of an antipseudomonal cephalosporin was 52.2%, but was lower for antipseudomonal penicillins (24.1%) and carbapenems (18.2%). Table 1 shows patient characteristics by exposure to the antibiotic classes of interest. The unadjusted and adjusted associations between the three antibiotic classes and aGVHD are shown in table 2. In the unadjusted model, high exposure to cephalosporins and carbapenems was statistically associated with increased aGVHD risk. For antipseudomonal penicillins, the direction of association was the same but not statistically significant. After adjustment, most point estimates reverted towards the null. The time to event analysis included 1,146 patients that were similar to the overall cohort with a similar incidence of aGVHD (35.5%) diagnosed a median of 28 (range: 8-100) days after HCT. This group had a higher proportion of mismatched donors (40.9 vs 30.2%), cord blood transplants (40.0 vs 23.5%) and receipt of growth factors (50.5% vs 38.9%). Table 2 also shows the unadjusted and adjusted associations for this analysis. As above, the unadjusted point estimates of association between cephalosporins and carbapenems and aGVHD were suggestive of an association but reverted towards the null with adjustment. Conclusions After controlling for other antibiotic exposures and GHVD-risk factors, there was not a statistically significant association between antibiotic exposure and aGVHD for any of three antibiotic classes commonly used for empiric therapy. However, the adjusted point estimates suggest exposure to carbapenems may confer some additional aGHVD risk. Further exploration of different exposure windows is planned to understand if the identified associations change with capture of earlier or later antibiotic exposures. Disclosures Jagasia: Kadmon: Consultancy; Incyte: Consultancy; Janssen: Research Funding. MacMillan:Alpine Immune Sciences: Consultancy; Angiocrine: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Equillium: Membership on an entity's Board of Directors or advisory committees. Fisher:Pfizer: Research Funding; Astellas: Other: Data Safety Monitoring Board Chair for an antifungal study; Merck: Research Funding.

Early antibiotics use in young infants with invasive bacterial infection visiting emergency department, a single medical center's experience

The Surviving Sepsis Campaign (SSC) recommends that intravenous antimicrobials be administered within one hour to treat sepsis in both adult and pediatric patients. However, most studies on the timing of antibiotics have been based on adults so far. Therefore, the goal of this study was to clarify the clinical outcomes of the timing of antibiotics use in young infants diagnosed with invasive bacterial infections. We conducted this retrospective, cohort study at a single tertiary medical center during the period of 2007-2013 and included young infants visiting the PED diagnosed with an invasive bacterial infection. Early antibiotics use is defined as broad-spectrum intravenous antibiotics given within one hour of a patient's triage at PED. In this study, we have analyzed the factors associated with early antibiotics use and measured such primary outcomes as mortality, ICU admission, ventilation support, and length of hospital stay. A total of 1231 visits of young infants with fever occurred during our study period, and we included 41 patients in our study; 29 of them were diagnosed with bacteremia and the remaining 12 with bacterial meningitis. Early antibiotics use was also associated with a shortened hospital stay (14±8.5 vs. 24±19.6; p=0.043). However, no statistical differences were observed with regard to mortality, ICU admission, or ventilation support. Among young infants that visited the pediatric department with an invasive bacterial infection, early broad-spectrum antibiotics use was not associated with reduced mortality rate, ICU admission, or ventilator support. However, it may have advantages regarding hospital length of stay.

Successful multi-disciplinary management of a 24 year old pregnant woman with necrotising fasciitis of the forearm

Introduction Necrotising fasciitis a relatively uncommon but rapidly progressive soft tissue infection. The incidence is 0.24-0.4 per 100,000. 1 This condition requires urgent aggressive surgical debridement and broad-spectrum antibiotics. Mortality from this condition has been quoted to be from 6-76%. 2 Sepsis can cause pre-term labour, fetal infection, and preterm delivery. The prevention of these complications is through early recognition and targeted therapy. This should include aggressive rehydration and broad-spectrum antibiotics, with an emphasis on stabilisation of the mother as a priority, as in doing so the foetal status will likewise improve. 3 Case description A 24-year-old woman who was 24 weeks pregnant presented to the emergency department with septic shock. She had injured the tip of her right elbow four days previously, causing a 0.5cm laceration which was now discharging pus. Her initial blood pressure was 84/43mmgHg, heart rate 110 beat per minute, serum C-reactive protein (CRP) was 392mg/L, and white cell count (WCC) 32x10 9 /L. She was initially given fluid resuscitation, and broad spectrum IV antibiotics. Through prompt coordinated prioritisation of the multi-disciplinary team, this lady was taken to theatre for prompt debridement. We found dirty dishwater fluid, and pus above the fascial layer up to the wrist. She improved dramatically after this. Results and Conclusions We have presented a case of necrotising fasciitis in a 24 year old pregnant woman whom had extremely early broad spectrum antibiotics and radical surgical debridement. We feel this lady was prioritised by several teams and her efficient, early, coordinated management led to an excellent outcome for both mother and child. Necrotising fasciitis is an uncommon condition with a high morbidity and mortality. Our patient had no risk factors for necrotising fasciitis aside from pregnancy. This may imply as McHenry 4 suggests, that pregnancy itself may cause an immunosuppressive state enough for it to be considered a risk factor for the disease. Take home message • Necrotising fasciitis/necrotising soft tissue infection is a clinical diagnosis. • Management in pregnancy is the same. • Management includes broad spectrum antibiotics and very early aggressive surgical debridement. • Senior surgical input should be sought early. • This is very rare in pregnancy and there are no reported upper limb cases of necrotising fasciitis.

The Emergency Medicine−Focused Review of Cholangitis

BackgroundCholangitis is a life-threatening infection of the biliary tract. Historically, the mortality secondary to cholangitis approached 100%. However, with early recognition, antibiotics, resuscitation, and surgical or endoscopic intervention, patient outcomes have significantly improved, although there is still progress to be made. Objective of ReviewThe objective of this review is to provide an emergency medicine−centered approach to the risk factors, presentations, and various diagnostic and treatment modalities in cholangitis. DiscussionEarly recognition and treatment of cholangitis in the emergency department is instrumental in ensuring a favorable outcome for patients. Recognition of acute cholangitis can be challenging, as many patients do not present with the classic symptoms of Charcot's triad. This article reviews the risk factors in cholangitis, as well as the typical presentations and necessary diagnostic studies. Furthermore, once diagnosis is made, distinguishing those requiring emergent biliary decompression from those who may tolerate a delayed procedure can also be difficult. Scoring systems that attempt to identify patients who may tolerate a delayed approach have yet to be validated. This review discusses the appropriate antibiotic therapy based on most common pathogens, as well as the options for achieving biliary decompression. ConclusionsCholangitis is a life-threatening infection that carries a high likelihood of poor outcomes if not treated early and aggressively in the emergency department. Appropriate recognition, early broad-spectrum antibiotics, and fluid resuscitation are paramount, and in patients with severe disease, early biliary decompression will significantly reduce mortality.

Systemic inflammatory response syndrome-based severe sepsis screening algorithms in emergency department patients with suspected sepsis.

Systemic inflammatory response syndrome (SIRS)-based severe sepsis screening algorithms have been utilised in stratification and initiation of early broad spectrum antibiotics for patients presenting to EDs with suspected sepsis. We aimed to investigate the performance of some of these algorithms on a cohort of suspected sepsis patients. We conducted a retrospective analysis on an ED-based prospective sepsis registry at a tertiary Sydney hospital, Australia. Definitions for sepsis were based on the 2012 Surviving Sepsis Campaign guidelines. Numerical values for SIRS criteria and ED investigation results were recorded at the trigger of sepsis pathway on the registry. Performance of specific SIRS-based screening algorithms at sites from USA, Canada, UK, Australia and Ireland health institutions were investigated. Severe sepsis screening algorithms' performance was measured on 747 patients presenting with suspected sepsis (401 with severe sepsis, prevalence 53.7%). Sensitivity and specificity of algorithms to flag severe sepsis ranged from 20.2% (95% CI 16.4-24.5%) to 82.3% (95% CI 78.2-85.9%) and 57.8% (95% CI 52.4-63.1%) to 94.8% (95% CI 91.9-96.9%), respectively. Variations in SIRS values between uncomplicated and severe sepsis cohorts were only minor, except a higher mean lactate (>1.6 mmol/L, P < 0.01). We found the Ireland and JFK Medical Center sepsis algorithms performed modestly in stratifying suspected sepsis patients into high-risk groups. Algorithms with lactate levels thresholds of >2 mmol/L rather than >4 mmol/L performed better. ED sepsis registry-based characterisation of patients may help further refine sepsis definitions of the future.

A review of 48 patients after bear attacks in Central India: Demographics, management and outcomes.

Introduction:Bear attacks though relatively rare are frequent enough to be of concern for those who are in bear habitats. Our centre at Nagpur, being surrounded by dense forests from all the sides, treats a large number of victims.Aim:The aim was to document the injuries, management and the potential complications of bear attacks.Materials and Methods:We reviewed the records of 48 consecutive patients who were treated in our department from January 2006 to December 2013 for bear attacks.Outcome:The majority of patients were referred 24-48 h post-attack. All but two patients had involvement of either the face or scalp. Involvement of eyes, mandible, facial nerve, was common. Reconstruction included simple suture of lacerations to management of complex compound injuries with three-dimensional defects. Thirteen patients developed infection.Conclusion:Bear attack victims need a multidisciplinary approach. Early broad spectrum antibiotics, anti-rabies prophylaxis and irrigation and debridement of the wound are needed. We advise early referral to tertiary treatment centres.

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Case Reports: Over the past decade, the use of focused transthoracic echocardiography (TTE) by intensivists to guide patient management has become increasingly popular. We present a complex case in which management was guided by focused TTE. A 60 y/o male with a history of Hodgkin’s lymphoma, pulmonary fibrosis, and mitral stenosis underwent video assisted left lower lobectomy and bronchoplasty for adenocarcinoma. Six days later he presented with a post obstructive pneumonia in the remaining left upper lobe. Despite early broad spectrum antibiotics, he progressed to ARDS and septic shock. He underwent urgent thoracotomy for washout and debridement of a left thoracic abscess. A central line was placed but a pulmonary artery (PA) catheter was avoided due to a thrombus in the PA stump. The patient suffered a PEA arrest in the OR immediately after reinflation of the lung, recovering after CPR and emergent re-thoracotomy. In the ICU the intensivist performed a focused bedside TTE to assess volume status, finding a relatively under filled, hypertrophied left ventricle (LV) with an enlarged left atrium (LA) and visibly stenotic mitral valve. This prompted an immediate switch from epinephrine to norepinephrine to enhance afterload and avoid tachycardia. The focused TTE findings were confirmed several hours later by a cardiology read ultrasound. The patient experienced two more episodes of severe hypotension following episodes of coughing or straining while on mechanical ventilation. Each time, TTE was performed immediately by the intensivist and demonstrated relatively under filled LV. Emergent paralysis was instituted based on the hypothesis that increases in intrathoracic pressure during movement and coughing had led to temporary loss of preload. This intervention led to immediate hemodynamic stabilization. In the following days the titration of catecholamines and diuretics was guided by focused TTE. This case report demonstrates the utility of focused TTE in the hands of a trained intensivist team as an effective tool to guide immediate management decisions in the acute care ICU setting.

Effectiveness of Treatments for Severe Sepsis

Several Surviving Sepsis Campaign Guidelines recommendations are reevaluated. To analyze the effectiveness of treatments recommended in the sepsis guidelines. In a prospective observational study, we studied all adult patients with severe sepsis from 77 intensive care units. We recorded compliance with four therapeutic goals (central venous pressure 8 mm Hg or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, central venous oxygen saturation 70% or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, blood glucose greater than or equal to the lower limit of normal but less than 150 mg/dl, and inspiratory plateau pressure less than 30 cm H(2)O for mechanically ventilated patients) and four treatments (early broad-spectrum antibiotics, fluid challenge in the event of hypotension and/or lactate greater than 36 mg/dl, low-dose steroids for septic shock, drotrecogin alfa [activated] for multiorgan failure). The primary outcome measure was hospital mortality. The effectiveness of each treatment was estimated using propensity scores. Of 2,796 patients, 41.6% died before hospital discharge. Treatments associated with lower hospital mortality were early broad-spectrum antibiotic treatment (treatment within 1 hour vs. no treatment within first 6 hours of diagnosis; odds ratio, 0.67; 95% confidence interval, 0.50-0.90; P = 0.008) and drotrecogin alfa (activated) (odds ratio, 0.59; 95% confidence interval, 0.41-0.84; P = 0.004). Fluid challenge and low-dose steroids showed no benefits. In severe sepsis, early administration of broad-spectrum antibiotics in all patients and administration of drotrecogin alfa (activated) in the most severe patients reduce mortality.

Ventilator-Associated Pneumonia: A Review

Ventilator-associated pneumonia is the most frequent intensive care unit (ICU)-related infection in patients requiring mechanical ventilation. In contrast to other ICU-related infections, which have a low mortality rate, the mortality rate for ventilator-associated pneumonia ranges from 20% to 50%. These clinically significant infections prolong duration of mechanical ventilation and ICU length of stay, underscoring the financial burden these infections impose on the health care system. The causes of ventilator-associated pneumonia are varied and differ across different patient populations and different types of ICUs. This varied presentation underscores the need for the intensivist treating the patient with ventilator-associated pneumonia to have a clear knowledge of the ambient microbiologic flora in their ICU. Prevention of this disease process is of paramount importance and requires a multifaceted approach. Once a diagnosis of ventilator-associated pneumonia is suspected, early broad-spectrum antibiotic administration decreases morbidity and mortality and should be based on knowledge of the sensitivities of common infecting organisms in the ICU. De-escalation of therapy, once final culture results are available, is necessary to minimize development of resistant pathogens. Duration of therapy should be based on the patient's clinical response, and every effort should be made to minimize duration of therapy, thus further minimizing the risk of resistance.

Current Concepts in Severe Sepsis and Septic Shock

Sepsis is a frequent cause of presentation to the emergency department (ED). Early identification and aggressive management in the ED is paramount to improving morbidity and mortality associated with sepsis. As a result, pharmacists in the ED should be familiar with and assist with the optimization of therapy for sepsis in this patient population. This article will discuss the epidemiology and economic impact of sepsis and the definitions, pathophysiology, and clinical presentation of sepsis and its related syndromes. In addition, the authors will discuss the elements related to treatment of sepsis from the Surviving Sepsis Campaign Guidelines that are particularly germane to the management of sepsis in the ED. Direct support such as source control, early broad-spectrum antibiotic therapy, hemodynamic assessment, and continuous monitoring are essential. In addition, early aggressive fluid resuscitation with titration of therapy to mixed venous oxygen saturation >70%, tight glycemic control and choice of vasopressors and inotropes have been shown to decrease mortality in sepsis. Mechanical ventilation with low tidal volumes, renal replacement therapies, early enteral nutritional support, and stress ulcer prophylaxis are also important considerations in septic patients. Controversies in therapy such as the utility of drotrecogin α activated, low-dose corticosteroids, and vasopressin are also discussed.

UPPER EXTREMITY INFECTIONS FOLLOWING COMMON CARP FISH (CYPRINUS CARPIO) HANDLING

Upper extremity infection caused by aquatic pathogens on fish is a well recognized clinical entity. We report five consecutive cases of upper extremity infections, ranging from a simple localized reaction to a life-threatening systemic illness, which developed after handling common carp fish (Cyprinus carpio). In four cases, infection occurred following a penetrating injury by either the bones or the fin spines of the fish. Vibrio vulnificus was isolated from wound aspirates in four cases. Early broad-spectrum antibiotic therapy is mandatory. Deterioration in the clinical condition or a poor response to conservative treatment requires a meticulous surgical drainage and excision of both infected and necrotic tissues.

Pathogenesis and Management of Septic Shock

Despite modern advances in antibiotic therapy and cardiovascular support, septic shock remains a condition plagued by a high mortality rate, estimated at 40- 60%. The pathogenesis of septic shock involves a complex orchestration of cytokines which lead to vasodilation, increased capillary permeability, and disturbances of metabolism. The major clinical features include hypotension, tissue hypoperfusion, myocardial depression, and organ failures. Cur-rent therapy focuses on early broad-spectrum antibiotic treatment, correction of hypovolemia, and appro-priate use of vasopressor and/or inotropic agents. Experimental attempts to intervene in the septic cytokine cascade hold promise, but none have shown a definitive clinical benefit. This review examines the pathogenesis, clinical features, current therapeutic approaches, and future prospects for this serious prob-lem.