Suryadi N. N. Tatura, Elizabeth Clarissa Wowor, Jose M. Mandei, Rocky Wilar, Sarah M. Warouw, Johnny Rompis, Priscilla Kalensang and Joseph Tuda

Abstract. Severe congenital malaria associated with Plasmodium vivax is uncommon. In Indonesia, most congenital malaria cases are due to Plasmodium falciparum infections. Most cases of congenital or neonatal malaria in endemic areas are diagnosed from peripheral smear as part of routine sepsis workup. Differentiating congenital and acquired neonatal malaria is very difficult. The case presented in this study describes severe P. vivax malaria with cholestatic jaundice and sepsis-like signs and symptoms in neonates. The mother was asymptomatic and the neonate was successfully treated with intravenous artesunate. Severe P. vivax malaria with cholestatic jaundice in neonates is an uncommon condition that should be included in the differential diagnosis of infants displaying hemolytic anemia, thrombocytopenia, cholestatic jaundice, and hepatosplenomegaly in malaria-endemic zones. Early diagnosis can prevent the use of unnecessary antibiotics and mortality of neonates.

Yoon, Jaechul; Kym, Dohern; Hur, Jun; Kim, Youngmin; Yang, Hyeong-Tae; Yim, Haejun; Suk Cho, Yong; Chun, Wook

Objectives: We evaluated the ability of new sepsis (S3) criteria (compared with previous definitions of sepsis [S1] and burn sepsis criteria) to accurately determine the mortality in severe burns patients with sepsis. Design: This was retrospective cohort study. Setting: The Burn ICU of Burn Center, Hangang Sacred Heart Hospital, Hallym University, Seoul, Korea. Patients: A total of 1,185 adult patients (mean age, 49.1 yr) were admitted between January 2009 and December 2015. Interventions: The 1,185 patients enrolled in the present study and were then re-evaluated based on S1, burn sepsis, and S3 criteria, following which 565 patients, 812 patients, and 809 patients were diagnosed with sepsis based on S1, burn sepsis, S3 criteria, respectively. Measurements and Main Results: For diagnostic performance, sensitivity, specificity, predictive value, and likelihood ratio were calculated. The area under the curve of the receiver operating characteristic curve was calculated to determine the accuracy of mortality prediction. The optimal cutoff value of Sequential Organ Failure Assessment score was calculated by the decision tree method.Total body surface area burned was 33.4%. Patients were identified with sepsis using S1 (812), S3 (809), and burn sepsis (565) criteria. Overall mortality was 20.3%, highest (82.2%) and lowest (26.5%) occurred with new septic shock (SH3) and S3, respectively. The sensitivity and specificity for burn sepsis (84.6% and 61.8%) and SH3 (63.1% and 96.5%) were reported. Area under the curve values for Sequential Organ Failure Assessment scores were the highest in all sepsis categories. With Sequential Organ Failure Assessment score greater than or equal to 6 (with infection), the accuracy was 0.86 (95% CI, 0.82–0.89). Conclusions: The S3 criteria failed to show superior prognostic accuracy for mortality in severely burned patients. Sequential Organ Failure Assessment score greater than or equal to 6 may be a better criterion for the diagnosis of sepsis in burns patients. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: dohern@hallym.or.kr Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Pelton, S. I.

Despite advances in treatment and prevention, the pneumococcus continues as a dominant cause of severe pneumonia and sepsis, of otitis media, sinusitis and nonbacteremic pneumonia. Lewnard and colleagues use a unique data set of nasopharyngeal and middle ear fluid samples to provide further insight into the progression of nasopharyngeal pneumococcal colonization to disease. They report the comparative rate of progression from colonization to otitis media by serotype, providing insight as to how conjugate vaccines that do not reduce the overall presence of pneumococci in the nasopharynx dramatically impact the incidence of acute and complex otitis media.

Skorup, Paul; Maudsdotter, Lisa; Tano, Eva; Lipcsey, Miklós; Castegren, Markus; Larsson, Anders; Sjölin, Jan

Objectives: To investigate the dynamics of antibiotic-induced endotoxin liberation and inflammatory response in vivo in a clinically relevant large animal intensive care sepsis model and whether the addition of an aminoglycoside to a β-lactam antibiotic affects these responses. Design: Prospective, placebo-controlled interventional experimental study. Setting: University research unit. Subjects: Thirty-six healthy pigs administered Escherichia coli as a 3-hour infusion. Interventions: After 2 hours, during E. coli infusion, the animals were exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or saline. Measurements and Main Results: Plasma endotoxin, interleukin-6, tumor necrosis factor-α, leucocytes, and organ dysfunction were recorded for 4 hours after antibiotic treatment, and differences to the values before treatment were calculated. In vitro experiments were performed to ascertain whether endotoxin is released during antibiotic-induced bacterial killing of this E. coli strain. Despite differences between the treatment arms in vitro, no differences in plasma endotoxin were observed in vivo. Antibiotic-treated animals demonstrated a higher interleukin-6 response (p < 0.001), greater leucocyte activation (p < 0.001), and more pronounced deterioration in pulmonary static compliance (p < 0.01) over time than controls. Animals treated with the combination showed a trend toward less inflammation. Conclusions: Treatment with antibiotics may elicit an increased inflammatory interleukin-6 response that is associated with leucocyte activation and pulmonary organ dysfunction. No observable differences were detected in plasma endotoxin concentrations. The reduction in cefuroxime-induced endotoxin release after the addition of an aminoglycoside in vitro could not be reproduced in this model. This study was performed at the Section for Clinical Research and at the Hedenstierna Laboratory, Uppsala University Hospital, Uppsala, Sweden. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by the R&D funds of Uppsala University and by the Olinder-Nielsen Family Fund for Research in Infectious Diseases. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail paul.skorup@medsci.uu.se Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Masse, Marie-Hélène; Richard, Marie Anne; D’Aragon, Frédérick; St-Arnaud, Charles; Mayette, Michael; Adhikari, Neill K. J.; Fraser, William; Carpentier, André; Palanchuck, Steven; Gauthier, David; Lanthier, Luc; Touchette, Matthieu; Lamontagne, Albert; Chénard, Jean; Mehta, Sangeeta; Sansoucy, Yanick; Croteau, Etienne; Lepage, Martin; Lamontagne, François

Objectives: Mechanisms underlying sepsis-associated encephalopathy remain unclear, but reduced cerebral blood flow, alone or in conjunction with altered autoregulation, is reported as a potential contributor. We compared cerebral blood flow of control subjects and vasopressor-dependent septic patients. Design: Randomized crossover study. Setting: MRI with arterial spin labeling. Patients: Ten sedated septic patients on mechanical ventilation (four with controlled chronic hypertension) and 12 control subjects (six with controlled chronic hypertension) were enrolled. Mean ± SD ages were 61.4 ± 10.2 and 44.2 ± 12.8 years, respectively (p = 0.003). Mean Acute Physiology and Chronic Health Evaluation II score of septic patients at ICU admission was 27.7 ± 6.6. Interventions: To assess the potential confounding effects of sedation and mean arterial pressure, we measured cerebral blood flow with and without sedation with propofol in control subjects and at a target mean arterial pressure of 65 mm Hg and greater than or equal to 75 mm Hg in septic patients. The sequence of sedation versus no sedation and mean arterial pressure targets were randomized. Measurements and Main Results: In septic patients, cerebral blood flow measured at a mean arterial pressure target of 65 mm Hg (40.4 ± 10.9 mL/100 g/min) was not different from cerebral blood flow measured at a mean arterial pressure target of greater than or equal to 75 mm Hg (41.3 ± 9.8 mL/100 g/min; p = 0.65). In control subjects, we observed no difference in cerebral blood flow measured without and with sedation (24.8 ± 4.2 vs 24.9 ± 5.9 mL/100 g/min; p = 0.93). We found no interaction between chronic hypertension and the effect of sedation or mean arterial pressure targets. Cerebral blood flow measured in sedated septic patients (mean arterial pressure target 65 mm Hg) was 62% higher than in sedated control subjects (p = 0.001). Conclusions: In septic patients, cerebral blood flow was higher than in sedated control subjects and did not vary with mean arterial pressure targets. Further research is required to understand the clinical significance of cerebral hyperperfusion in septic patients on vasopressors and to reassess the neurologic effects of current mean arterial pressure targets in sepsis. This work was performed at Centre de recherche du CHUS, Sherbrooke, QC, Canada. Dr. F. Lamontagne conceived the study. Ms. Masse, Ms. Richard, and Drs. D’Aragon, Palanchuck, Lepage, and F. Lamontagne initiated the study design. Drs. St-Arnaud, Mayette, Adhikari, Fraser, Carpentier, Gauthier, Lanthier, Touchette, A. Lamontagne, Chénard, Mehta, Sansoucy, and Croteau helped with implementation. Drs. D’Aragon, Fraser, Carpentier, Sansoucy, Lepage, and F. Lamontagne are grant holders. Drs. Adhikari and F. Lamontagne provided statistical expertise in clinical trial design. All authors contributed to refinement of the study protocol and approved the final article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grant from the Centre de Recherche du CHUS. Drs. D’Aragon, Fraser, Carpentier, Palanchuck, Gauthier, Croteau, Lepage, and F. Lamontagne members of the Fonds de recherche du Québec-Santé funded CRCHUS. Dr. Mayette received support for article research from local funding. Dr. Carpentier’s institution received funding for consulting from UniQure Biopharma, Siemens Healthcare/Molecular Imaging, and Janssen; for research grants from Merck Sharpe and Dome (UdeS), GlaxoSmithKline (chair), Janssen, UniQure Biopharma, Caprion (Canadian Institutes Health Research University of Toronto), and Jonhson & Jonhson; for invited speaker fees from Siemens Healthcare/Molecular Imaging, Merck, Amgen, UniQure, and Medtronic; for sponsored research from Hamilton Health Research, Novartis, AstraZeneca, BMS, Sanofi Aventis, Merck, Pfizer, NovoNordisk, The Medicine Companies, Exelixis, Amgen, and UniQure Biopharma; and for sponsorship for scientific events from Siemens, Amgen, Merck, Takeda, Pfizer, Agilent, Janssen, NovoNordisk, Boehringer Lilly, AstraZeneca, Sanofi, Amgen, Aegerion, and Financière Sun Life. Dr. Lepage received support for article research from pilot institutional funding. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Francois.Lamontagne@USherbrooke.ca Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Deep, Akash; Sagar, Hiremath; Goonasekera, Chulananda; Karthikeyan, Palaniswamy; Brierley, Joe; Douiri, Abdel

Objectives: There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock. Design: Prospective cohort study. Setting: PICU of a tertiary care hospital. Patients: All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014. Interventions: Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury. Measurements and Main Results: Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52–6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3–99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury. Conclusions: Manifestations of sepsis-associated acute kidney injury often occur early after PICU admission and is associated with increased morbidity and mortality. There is a need to develop a predictive model in septic shock which could facilitate early detection of acute kidney injury. This work was performed at King’s College Hospital, Denmark Hill, London SE5 9RS, United Kingdom. Ethical Statement: This was an observational study of routinely monitored hemodynamic and biochemical variables in the clinical management of children in septic shock in PICU and their outcomes. All children received standard therapies. Therefore, according to local guidelines, Ethics Committee review was not required. However, this study was registered as a service evaluation project at King’s College Hospital (Clinical Audit Support System project no. 2902). Dr. Deep is the supervisor who conceptualized the project and supervised data collection, interpretation and has reviewed and edited the article. He is the corresponding author. Drs. Sagar and Karthikeyan collected the data and contributed to the initial article. Drs. Goonasekera and Brierley helped edit the article. Dr. Douiri is senior lecturer of Biostatistics and Epidemiology in the department of primary care and public health sciences at King’s College London who advised the statistical design and analysis of the data. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Douiri acknowledges financial support from the National Institute for Health Research (NIHR) Biomedical Research and from the NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Akash Deep, MD, FRCPCH, PICU, King’s College Hospital, Denmark Hill, London SE5 9RS, United Kingdom. E-mail: akash.deep@nhs.net Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Raoultella ornithinolytica is increasingly being isolated as a causative organism in human infections. Most of the infections caused by R. ornithinolytica are hospital acquired and occur in patients who are immunocompromised, had invasive procedures or have indwelling catheters. This is a first report of early onset neonatal sepsis caused by multi-drug-resistant R. ornithinolytica. The infection was not very severe and was characterised by generalized flushing of the skin. Patient made complete recovery once appropriate antibiotics were started.

Chan, E., Martelli, P., Hui, S.-W., Teng, J. L. L., Lau, S. K. P., Woo, P. C. Y.

Burkholderia pseudomallei is the cause of melioidosis, a potentially serious and fatal disease characterized by community-acquired pneumonia and/or sepsis mainly in Southeast Asia and Northern Australia, and high case-fatality rates of up to 19% are observed in endemic areas (1).

Brendon P. Scicluna

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 1070-1073, April 15, 2018.

Abstract Background Congenital malaria is the direct infection of an infant with malaria parasites from their mother prior to or during birth. Neonatal malaria is due to an infective mosquito bite after birth. Neonatal and congenital malaria (NCM) are potentially life-threatening conditions that are believed to occur at relatively low rates in malaria endemic regions. However, recent reports suggest that the number of NCM cases is increasing, and its epidemiology remains poorly described. NCM can mimic other neonatal conditions and because it is thought to be rare, blood film examinations for malaria are not always routinely performed. Consequently, many cases of NCM are likely to be undiagnosed. A retrospective chart review for all neonates admitted with suspected sepsis between January and July 2017 was conducted and noted four cases of NCM since routine malaria testing was introduced as part of standard of care for suspected sepsis at Mbale Regional Referral Hospital Neonatology Unit. This description highlights the need to conduct routine malaria diagnostic testing for febrile neonates in malaria endemic areas, and supports the urgent need to undertake pharmacological studies on therapeutic agents in this population. Case presentation Four cases (two congenital malaria cases and two neonatal malaria cases) are described after presenting for care at the Mbale Regional Referral Hospital Neonatal Unit (Mbale RRH-NNU). The maternal age was similar across the cases, but both neonatal malaria cases were born to primigravidae. At presentation three cases had fever and history of fever, but one was hypothermic (34.8 °C) and no history of fever. One case of congenital malaria had low birth weight, while the other was born to an HIV positive mother. Both cases of congenital malaria presented with poor feeding, in addition one of them had clinical jaundice. The neonatal malaria cases presented in the third week compared to the congenital malaria cases that presented within 48 h after birth. All of the cases of NCM were treated with intravenous artesunate. The admitting clinicians also instituted a course of antibiotics empirically to cover against possible bacterial co-infections. All four cases recovered and were discharged alive. Conclusion At the Mbale RRH-NNU, the finding of cases of NCM was not expected, therefore, neonates presenting with features of suspected sepsis in malaria endemic settings should be routinely screened for NCM. There is currently a lack of appropriate guidelines for treatment of NCM in the era of artemisinin-based combination therapy (ACT), therefore, efforts to establish the safety profile and efficacy of ACT anti-malarials in neonates to guide development of evidence-based treatment guidelines for NCM are needed.

Padari, H., Metsvaht, T., Germovsek, E., Barker, C. I., Kipper, K., Herodes, K., Standing, J. F., Oselin, K., Tasa, T., Soeorg, H., Lutsar, I.

Group B streptococci are common causative agents of early-onset neonatal sepsis (EOS). Pharmacokinetic (PK) data for penicillin G have been described for extremely preterm neonates but poorly for late-preterm and term neonates. Thus, evidence-based dosing recommendations are lacking. We described PK of penicillin G in neonates with gestational age (GA) ≥32 weeks and postnatal age 90% for MICs ≤2 mg/L with doses of 25,000 IU/kg/q12h. In neonates, regardless of GA, PK parameters of penicillin G are similar. The dose of 25,000 IU/kg/q12h is suggested for treatment of group B streptococcal EOS diagnosed within the first 72 hours of life.

Hampton T.

Previous research has shown platelets are involved in the innate immune response to pathogens via toll-like receptor expression, and evidence is emerging that they may also be important for adaptive immunity. A new study published in the Proceedings of the National Academy of Sciences has uncovered an unappreciated role of platelets in antibody-mediated adaptive immune responses.

A. Heffernan, J. Lipman, J. Roberts

We read with interest the comments from Ong et al. [1] regarding the need for a well-designed randomized controlled trial (RCT) to provide evidence to guide clinicians regarding the use of combined β-lactam antibiotic and aminoglycoside therapy for the management of critically ill patients with sepsis or septic shock. We would like to highlight the importance of appropriate dosing strategies and the inclusion of pharmacokinetic/pharmacodynamic (PK/PD) sub-studies to provide further evidence about the potential utility of combination therapy.

Vichaya Suttisunhakul, Phireak Hip, Pidor Ouch, Piseth Ly, Chonthida Supaprom, Agus Rachmat, Michael Prouty, Andrew Vaughn, Ahreej Eltayeb, Sim Kheng, Danielle V. Clark, James V. Lawler, Narisara Chantratita, Mary N. Burtnick, Paul J. Brett and Kevin L. Schully

Abstract. Burkholderia pseudomallei, the etiologic agent of melioidosis, is predicted to be ubiquitous in tropical regions of the world with areas of highest endemicity throughout Southeast Asia (SEA). Nevertheless, the distribution of B. pseudomallei and the burden of melioidosis in many SEA countries remain unclear. In Cambodia, only two human endemic cases of melioidosis were reported through 2008 and since then only a few hundred cases have been described in the literature. This is in sharp contrast to the annual burden of thousands of cases in surrounding areas. To further investigate the prevalence of melioidosis in Cambodia, we used a recently developed O-polysaccharide–based rapid enzyme-linked immunosorbent assay to detect B. pseudomallei–specific antibodies in serum samples obtained from 1,316 febrile illness or sepsis patients from 10 different provinces. Based on a cutoff value derived through culture-confirmed melioidosis cases, the proportion of positive samples in our cohort was approximately 12%. Regression analysis indicated that the odds of obtaining a positive result were 2.2 times higher for males than females controlling for age and province (95% confidence interval: 1.6–3.2, P < 0.001). Consistent with this, 9.2% of females were positive versus 18.2% of males (P < 0.001). Notably, 22.5% of grain or rice farmers were positive versus 10.1% of subjects with occupations not involving regular contact with soil. Positive results varied significantly by province. Collectively, the results of this study suggest that the true burden of melioidosis in Cambodia is greater than has previously been reported.

Mathieu, Calypso; Desrois, Martine; Kober, Frank; Lalevée, Nathalie; Lan, Carole; Fourny, Natacha; Iché-Torres, Magali; Tran, Thi Thom; Lê, Linh Thuy; Singer, Mervyn; Mège, Jean-Louis; Bernard, Monique; Leone, Marc

Objectives: To investigate any gender effect of the beta-1 adrenergic blocker, landiolol, on cardiac performance and energy metabolism in septic rats, and to explore the expression of genes and proteins involved in this process. Design: Randomized animal study. Setting: University research laboratory. Subjects: Male and female Wistar rats. Interventions: One hour after cecal ligation and puncture, male and female rats were randomly allocated to the following groups: sham male, cecal ligation and puncture male, cecal ligation and puncture + landiolol male, sham female, cecal ligation and puncture female, and cecal ligation and puncture + landiolol female. Cardiac MRI was carried out 18 hours after cecal ligation and puncture to assess in vivo cardiac function. Ex vivo cardiac function measurement and 31P magnetic resonance spectroscopy were subsequently performed using an isovolumic isolated heart preparation. Finally, we assessed cardiac gene and protein expression. Measurements and Main Results: In males, landiolol increased indexed stroke volume by reversing the indexed end-diastolic volume reduction without affecting left ventricle ejection fraction. In females, landiolol did not increase indexed stroke volume and indexed end-diastolic volume but decreased left ventricle ejection fraction. Landiolol had no effect on ex vivo cardiac function and on high-energy phosphate compounds. The effect of landiolol on the gene expression of natriuretic peptide receptor 3 and on protein expression of phosphorylated-AKT:AKT ratio and endothelial nitric oxide synthase was different in males and females. Conclusions: Landiolol improved the in vivo cardiac performance of septic male rats while deleterious effects were reported in females. Expression of natriuretic peptide receptor 3, phosphorylated-AKT:AKT, and endothelial nitric oxide synthase are signaling pathways to investigate to better understand the sex differences in sepsis. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by Fondation pour la Recherche Médicale (DEA 20150633224), AOP Orphan, Lions Club Marseille Doyen and France Life Imaging (grant ANR-11-INBS-0006). Dr. Mathieu received funding from Fondation Recherche Médicale (DEA20150633224) and Lions club Marseille Doyen. Dr. Singer received funding from AOP Pharma. Dr. Mege disclosed government work. Dr. Leone’s institution received funding from AOP Orphan (provided treatment: landiolol). The remaining authors do not have any potential conflicts of interest. For information regarding this article, Email: marc.leone@ap-hm.fr Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Purpose St. John of the Cross (1542–1591) died aged 49 years after 3 months of excruciating pain following a trivial lesion in his right foot. Erysipelas, a superficial bacterial infection of the skin, and subsequent sepsis were previously suggested as the cause of his death. Here, an alternative diagnosis is proposed. Methods An accurate perusal of his biography allowed the symptomatology, the clinical evolution, the depth of the infection and the associated systemic manifestations displayed by Fray John to be reconstructed. Results St. John of the Cross developed cellulitis in the foot, which turned into a cutaneous abscess. To treat the toxaemia and inhibit further necrosis of the skin, excision of necrotic tissue and cauterization of the sores were performed to no avail. The infection burrowed through the fascial planes and reached the bones of the leg, leading to osteomyelitis. Conclusions In the absence of antibiotic treatments and proper antiseptic procedures, the soft-tissue infection spread deeper to the bones. It is not unconceivable that the surgery might have further promoted the spread of the bacteria giving rise to the secondary sepsis that led to St. John’s premature death.

Timothy Barkham, Anna Sheppard, Nicola Jones, Swaine Chen

Sarah Masson-Roy

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 8, Page 985-986, April 15, 2018.

B. Lamy, M. Sundqvist

In May 2017, the World Health Assembly, the decision-making body of the World Health Organization (WHO), adopted a resolution on improving the prevention, diagnosis and treatment of sepsis, the most severe manifestation of acute infection, and an important but often unmarked healthcare issue [1,2]. Encouragingly, a reduction in sepsis-caused mortality has been reported in high-income countries following adoption of comprehensive guidelines such as the ‘Surviving Sepsis Campaign‘ [3]. However, these improvements are challenged by a 5–8% annual increase in the incidence of sepsis, a continuous increase of antibiotic resistance, and the long time taken to receive diagnostic results.

J. Rello, T.S.R. van Engelen, E. Alp, T. Calandra, V. Cattoir, W.V. Kern, M.G. Netea, S. Nseir, S.M. Opal, F.L. van de Veerdonk, M.H. Wilcox, W.J. Wiersinga

Our current understanding of the pathophysiology and management of sepsis is associated with a lack of progress in clinical trials, which partly reflects insufficient appreciation of the heterogeneity of this syndrome. Consequently, more patient-specific approaches to treatment should be explored.