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Although the disease is an important cause of mortality in the region, most published reports on bacterial meningitis in East Africa are from urban referral hospitals. Poor laboratory facilities make diagnosis difficult in the area and treatment is limited to inexpensive antibiotics. The case-fatality 'rate' in one rural hospital in Tanzania, the Ndala Mission Hospital (NMH), appears to have increased dramatically over recent years, perhaps as the result of increasing resistance to ampicillin and chloramphenicol. The aim of the present study, which was partially retrospective and partially prospective, was to review the number, characteristics and outcome of children admitted to this hospital with bacterial meningitis and to investigate possible resistance of the causative micro-organisms to the antibiotics used. Data from the 181 children who were admitted with bacterial meningitis [confirmed by the examination of Gram-stained smears of cerebrospinal fluid (CSF)] between 1999 and 2002 were retrospectively reviewed. The overall mortality among these children was 51%. No seasonal pattern was observed in the number of cases. In a 2-month prospective study in 2002, CSF samples from 19 consecutive cases were collected in Trans-Isolate medium and shipped to the Academic Medical Center in Amsterdam for culture and analysis of antibiotic susceptibility. For only eight (42%) of the cases was there agreement between the species of bacterium identified, by Gram-staining, in Tanzania and that identified, by culture, in The Netherlands. As there was no evidence of resistance to ampicillin and the antibiotics used in the NMH were found to be of good quality, the cause of the high mortality in the NMH remains uncertain. Poor laboratory testing, long doctor-patient delays and/or poor drug administration on the wards may all be contributory factors. Attempts will now be made to address each of these problems. [ABSTRACT FROM AUTHOR]

Sepsis remains a critical global health issue, demanding novel therapeutic strategies. Traditional immunomodulation treatments such as corticosteroids, specific modifiers of cytokines, complement or coagulation, growth factors or immunoglobulins, have so far fallen short. Meanwhile the number of studies investigating non-conventional immunomodulatory strategies is expanding. This review provides an overview of adjunctive treatments with herbal-based medicine, immunonutrition, vasopressors, sedative treatments and targeted temperature management, used to modulate the immune response in patients with sepsis. Herbal-based medicine, notably within traditional Chinese medicine, shows promise. Xuebijing injection and Shenfu injection exhibit anti-inflammatory and immune-modulatory effects, and the potential to lower 28-day mortality in sepsis. Selenium supplementation has been reported to reduce the occurrence of ventilator-associated pneumonia among sepsis patients, but study results are conflicting. Likewise, the immune-suppressive effects of omega-3 fatty acids have been associated with improved clinical outcomes in sepsis. The immunomodulating properties of supportive treatments also gain interest. Vasopressors like norepinephrine exhibit dual dosage-dependent roles, potentially promoting both pro- and anti-inflammatory effects. Dexmedetomidine, a sedative, demonstrates anti-inflammatory properties, reducing sepsis mortality rates in some studies. Temperature management, particularly maintaining higher body temperature, has also been associated with improved outcomes in small scale human trials. In conclusion, emerging non-conventional immunomodulatory approaches, including herbal medicine, immunonutrition, and targeted supportive therapies, hold potential for sepsis treatment, but their possible implementation into everyday clinical practice necessitates further research and stringent clinical validation in different settings. [ABSTRACT FROM AUTHOR]

While the 6-day group indeed contained somewhat more patients with recurrent disease - although this difference was not statistically significant and had no significant interaction effects with the outcome - it is unlikely that these patients suffered from cellulitis mimicry since they all initially responded to antibiotic therapy. Relapses would be incomparable when patients have therapy durations other than the ones in the study protocol. However, we would like to once again emphasize the fact that the patients included in that trial were relatively young patients treated on an outpatient basis. [Extracted from the article]

To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis. This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90. Between August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12- and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: –15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI: –8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05). Given the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies. [ABSTRACT FROM AUTHOR]

Abstract Background 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. Aims To summarize the current evidence on precision medicine in sepsis, with an emphasis on translation from theory to clinical practice. A secondary objective is to develop a framework enclosing recommendations on management and priorities for further research. Sources A global search strategy was performed in the MEDLINE database through the PubMed search engine (last search December 2017). No restrictions of study design, time, or language were imposed. Content The focus of this Position Paper is on the interplay between therapies, pathogens, and the host. Regarding the pathogen, microbiologic diagnostic approaches (such as blood cultures (BCs) and rapid diagnostic tests (RDTs)) are discussed, as well as targeted antibiotic treatment. Other topics include the disruption of host immune system and the use of biomarkers in sepsis management, patient stratification, and future clinical trial design. Lastly, personalized antibiotic treatment and stewardship are addressed (Fig. 1). Implications A road map provides recommendations and future perspectives. RDTs and identifying drug-response phenotypes are clear challenges. The next step will be the implementation of precision medicine to sepsis management, based on theranostic methodology. This highly individualized approach will be essential for the design of novel clinical trials and improvement of care pathways. [ABSTRACT FROM AUTHOR]