Thwaites C. Louise, Lundeg Ganbold, Dondorp Arjen M., Adhikari Neill K. J., Nakibuuka Jane, Jawa Randeep, Mer Mervyn, Murthy Srinivas, Schultz Marcus J., Thien Binh Nguyen, Kwizera Arthur
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
Nuffield Department of Clinical Medicine, Oxford Centre for Tropical Medicine and Global Health, Oxford, UK
Recommendations on the management of infections in patients with sepsis and septic shock are mainly derived from studies on bacterial sepsis in high-income settings and are not necessarily applicable elsewhere due to differences in etiology and diagnostic or treatment capacity. In this chapter, we provide recommendations on infection management in resource-limited ICUs, taking into account relevant contextual factors such as the availability, affordability, and feasibility of interventions. We empirical antibiotic therapy in patients with sepsis should cover all expected pathogens and likely resistance patterns, based on locally acquired epidemiological data as large regional variations exist. Limited availability of certain classes of antibiotics can complicate implementation of this. We that research groups in collaboration with stakeholders provide microbiological data from sentinel sites throughout resource-limited settings to guide local empirical antibiotic choices. There is weak evidence from resource-limited settings suggesting timely administration of antibiotics is beneficial. Observational data suggest that, in many resource-limited settings, the administration of antibiotics to most patients within 1 h of sepsis or septic shock recognition is feasible. Therefore, given biological plausibility and evidence from resource-rich settings, w appropriate antibiotics should be given within the first hour following sepsis or septic shock recognition. In resource-limited settings, microbiological laboratory facilities are often restricted, but there was evidence from these settings that taking blood cultures was associated with improved outcome in sepsis and septic shock and with improved appropriateness of antibiotics. We that blood cultures should be taken before the administration of antibiotics in locations where this is possible. Ideally, two sets of blood cultures should be obtained, although the additional yield has not been assessed in resource-limited settings. It is realized that in many hospitals, routine blood culture is unfeasible and expanding microbiological laboratory capacity could improve care. Identification of an infection source and source control are additional challenges in resource-limited settings and are affected by the facilities available. There was weak evidence of reasonable sensitivity of both chest radiography and ultrasound in the diagnosis of abdominal hollow viscus perforation (mainly studied in typhoid or tuberculosis) and abscesses in melioidosis. We found weak evidence that timely surgery was beneficial in typhoidal gastrointestinal perforations. Because of lack of published evidence, we do not provide specific recommendations on the use of chest radiography or ultrasound in resource-limited settings. We that source control is carried out within 12 h of admission to hospital, except in the specific case of pancreatic necrosis, where there is evidence from resource-rich settings that delay in surgical intervention may be beneficial. Combination antimicrobial therapy increases healthcare costs and toxicity. Current SSC guidelines only recommend combination therapy in specific situations, such as when the chances of multidrug resistance are high. Evidence in multidrug-resistant or extensively drug-resistant bacteria was confined to studies of infection, where combination therapy was beneficial. Where the chances of multidrug resistance are high, combination antibiotics should be considered. Choice of combination therapy should be guided by local epidemiology and known effective combinations. Antimicrobial therapy should be de-escalated whenever possible. It is recognized that without microbiological information, de-escalation is difficult. The use of biomarkers such as procalcitonin to guide de-escalation of antimicrobial therapy is promising but needs further assessment in resource-limited settings before a recommendation can be made. In conclusion, large variations in disease etiology and high rates of antimicrobial resistance combined with restricted choice of antibiotics and limited microbiological data pose significant challenges in the management of septic patients in resource-limited settings. Increased use of combination therapy and broad-spectrum antibiotic risks increases antimicrobial resistance. Enhanced surveillance necessitates better collaboration between stakeholders and improved microbiological facilities, which in turn requires significant investment. However, newer technologies which negate the need for specialist staff and equipment may become more available. This would not only improve the management of individual patients but, by providing high-quality epidemiological data, may help combat the global threat of antimicrobial resistance.
关于脓毒症和感染性休克患者感染管理的建议主要来自高收入环境下对细菌性脓毒症的研究，由于病因以及诊断或治疗能力的差异，这些建议不一定适用于其他地方。在本章中，我们考虑到干预措施的可获得性、可承受性和可行性等相关背景因素，提供了资源有限的重症监护病房（ICU）中感染管理的建议。鉴于存在较大的区域差异，我们认为脓毒症患者的经验性抗生素治疗应基于当地获得的流行病学数据，覆盖所有预期病原体和可能的耐药模式。某些类别的抗生素供应有限可能会使这一措施的实施复杂化。我们建议研究小组与利益相关者合作，提供来自整个资源有限地区哨点的微生物学数据，以指导当地的经验性抗生素选择。资源有限地区的证据薄弱，表明及时使用抗生素是有益的。观察数据表明，在许多资源有限的环境中，在识别脓毒症或感染性休克后1小时内对大多数患者使用抗生素是可行的。因此，鉴于生物学合理性以及资源丰富地区的证据，我们建议在识别脓毒症或感染性休克后的第一小时内给予适当的抗生素。在资源有限的环境中，微生物实验室设施往往受限，但这些环境中的证据表明，采集血培养与改善脓毒症和感染性休克的结局以及提高抗生素使用的合理性相关。我们建议在可能的情况下，在使用抗生素之前采集血培养。理想情况下，应采集两套血培养，尽管在资源有限的环境中尚未评估额外采集的收益。人们意识到，在许多医院，常规血培养不可行，扩大微生物实验室能力可能会改善治疗。识别感染源和进行源控制在资源有限的环境中是额外的挑战，并且受到可用设施的影响。有薄弱证据表明，胸部X线摄影和超声对腹部中空脏器穿孔（主要在伤寒或结核病中研究）和类鼻疽脓肿的诊断具有合理的敏感性。我们发现有薄弱证据表明，及时手术对伤寒性胃肠道穿孔有益。由于缺乏已发表的证据，我们未就资源有限环境中胸部X线摄影或超声的使用提供具体建议。我们建议在入院后12小时内进行源控制，但胰腺坏死的特定情况除外，在资源丰富地区有证据表明手术干预延迟可能是有益的。联合抗菌治疗会增加医疗成本和毒性。当前的拯救脓毒症运动（SSC）指南仅在特定情况下推荐联合治疗，例如多重耐药可能性高时。多重耐药或广泛耐药细菌的证据仅限于对[具体感染]的研究，联合治疗在该研究中是有益的。在多重耐药可能性高的情况下，应考虑联合使用抗生素。联合治疗的选择应根据当地流行病学和已知有效的联合方案来指导。只要有可能，抗菌治疗就应降级。人们认识到，在没有微生物学信息的情况下，降级很难。使用生物标志物如降钙素原指导抗菌治疗的降级很有前景，但在资源有限的环境中还需要进一步评估才能提出建议。总之，疾病病因的巨大差异、高抗菌耐药率、抗生素选择受限以及微生物学数据有限，给资源有限环境中脓毒症患者的管理带来了重大挑战。联合治疗和广谱抗生素使用风险的增加会加剧抗菌耐药性。加强监测需要利益相关者之间更好的合作以及改善微生物学设施，这反过来又需要大量投资。然而，无需专业人员和设备的新技术可能会更普及。这不仅会改善个体患者的管理，还会通过提供高质量的流行病学数据，有助于应对抗菌耐药性的全球威胁。
