Research progress on application of lactoferrin in clinical field / 中国生物制品学杂志

@#Lactoferrin(LF),as a kind of iron-bound natural transferrin with wide functions,has become a research hotspot at home and abroad in recent years. Studies have shown that LF has a wide range of treatment,prevention and biological activity. This paper reviewed the clinical effects of LF in immune regulation,anti-tumor,regulation of obesity mechanism,antibacterial,anti-Alzheimer disease(AD)and bone regeneration mechanism in recent years,in order to provide a direction for the follow-up clinical application and research of LF.

Meta-analysis of the effect of procalcitonin on anti-infection treatment in the elderly / 中华老年医学杂志

Objective:To evaluate the effect of procalcitonin(PCT)guiding anti-infection therapy on the prognosis of elderly patients.Methods:By searching PubMed, EMBASE database, Cochrane library, Cochrane clinical trial center registry and SinoMed database in Chinese, we searched for a randomized controlled clinical(RCT)study on the effect of PCT-guided anti-infection treatment on the prognosis of elderly patients, which was conducted according to the PRISMA statement.The main purpose of the study was to evaluate the time of antibiotic application.Results:After retrieval, 9 RCT clinical studies were finally included, involving 2 702 elderly patients, with an average follow-up of 3.5 months(1-12 months). The average age was(71.3±8.9)years old, with 52.8% of males and baseline levels of white blood cell(WBC)was 12.9×10 9/L, C-reactive protein(CRP)was 18.9 mg/L, PCT was 0.38 μg/L.Compared with conventional anti-infective therapy, PCT-guided anti-infective therapy can reduce the antibiotic application time of elderly patients[standard mean difference( SMD)=-2.39 days, 95% CI(-4.03, -0.75)days, P=0.004]. However, PCT-guided anti-infection treatment had no significant effect on the length of hospital stay[ SMD=-0.46 d, 95% CI(-0.05, 0.14)d, P=0.135], the rate of reinfection[ RR=0.87, 95% CI(0.73, 1.03), P=0.105]and the risk of all-cause death[ RR=1.02, 95% CI(0.80, 1.31), P=0.863]. Conclusions:PCT-guided anti-infection treatment can reduce the time of antibiotic application in elderly patients, but other clinical effects need to be verified by more large-scale studies

Design, synthesis and biological evaluation of 8-hydroxyquinoline derivatives as potential clostridium difficile antibiotics / 药学实践杂志

Objective To find a more effective alternative therapy for antibiotic therapy and fecal microbiota transplantation in current primary treatment of clostridioides difficile infection (CDI) because of the high recurrence rate. Methods A series of 8-hydroxyquinoline derivatives were designed and synthesized based on 8-hydroxyquinoline scarffold. Results The activity test against C. difficile showed that most of the molecules exhibited good antibacterial activity against C. difficile, and compound 6f showed attractive anti-C. difficile activity. Conclusion A new type of 8-hydroxyquinoline derivatives with anti-clostridium difficile was found, which could be used as good lead compounds for further development.

Research progress on synthesis, safety, function and mechanism of selenium nanoparticles / 中国药理学通报

As an essential trace element, selenium plays a very important role in antioxidation and maintaining redox homeostasis in various metabolic processes. With the development of nano-technology, selenium nanoparticles ( SeNPs) have become potential biomedical drugs because of their low toxicity, degrad-ability and high bioavailability. With the ability to activate apop-tosis or autophagy by regulating the production of reactive oxygen species ( ROS) , SeNPs are widely used in anticancer therapy and pathogens killing/clearance. In addition, with excellent stability and drug encapsulation capacity, SeNPs are serving as a kind of effective nano-carriers for anti-cancer and anti-infection treatments. Interestingly, the important role of SeNPs in immune regulation ( such as the activation of macrophages and T effector cells) provides a new possibilities to achieve nano-immune syn-ergetic treatment strategy for anti-cancer and anti-infection thera¬pies. In this paper, we review the latest progress of the prepara¬tion methods and safety for SeNPs, followed by the advances of anti-infection, anti-cancer effects and its mechanisms, which would be helpful for promoting the pace of clinical research and application. In addition, we also summarize the functions of SeNPs in other aspects, so as to provide beneficial assistance for facilitating its scientific and clinical research.

Clinical application progress of granulocyte transfusion / 中国输血杂志

Granulocyte is granular leukocytes in blood, which play an important role in anti-infection treatment and cancer-killing activity. In clinical, allogeneic granulocyte transfusion can be applied for anti-infection treatment when the patients are seriously infected but the antibiotic treatment is ineffective, especially the WBC counts are extremely low. Recently, some progress has been made in the researches about treating cancer with granulocyte infusion. It is possible to use allogeneic granulocyte infusion with high killing activity to treat the certain types of cancers.

Treatment analysis and pharmaceutical care for one child with bacterial meningitis / 药学实践杂志

Objective To explore the strategies of drug treatment and pharmaceutical care for children with bacterial meningitis. Methods The anti-infective therapy, therapeutic drug monitoring and dose adjustment of vancomycin in children with bacterial meningitis were analyzed and discussed according to relevant guidelines and literatures. Results Clinical pharmacists analyzed therapeutic regimen. According to the results of etiology and drug sensitivity, meropenem was discontinued and rifampicin was added. Based on drug monitoring of vancomycin, it is suggested to extend the infusion time of vancomycin to reach the target concentration. The child was discharged from hospital. Conclusion Recommendations of the relevant drug treatment guidelines and the latest medical research evidence should be provided by clinical pharmacists in order to promote reasonable and effective clinical uses of medicine.

Optimization of Anti-infective Program after Surgery for a Case of Infant Patient with Intussusception and Enterobrosis by Clinical Pharmacists / 中国药房

OBJECTIVE：To provide th e ideas a nd for individualized anti-infective treatment of infection after surgery for infants and young children with intussusception and enterobrosis ，and to provide reference for clinical pharmacists participating in the clinical treatment. METHODS ：Clinical pharmacists optimized the anti-infection program for an 11-month-old infant patient infected after surgery with intussusception and enterobrosis in Ordos Central Hospital ；they put forward medication suggestions in respects of the selection of initial anti-infection treatment program ，drug replacement ，the selection of anti-infection treatment program after blood culture showed Enterococcus coli and Enterococcus faecium ，and dosage adjustment. RESULTS ：According to the judgment of the common pathogens and the hospital or community infections in the infant patient with intussusception and enterobrosis，cefoperazone sulbactam 1.0 g，q12 h was adjusted to cefoperazone sulbactam 0.5 g，q8 h combined with Metronidazole chloride sodium injection 20 mL，q8 h；when the blood culture showed E. coli （ESBL-）and E. faecium ，it was recommended to add vancomycin 0.15 g，q12 h. After poor treatment ，it was recommended to adjust the vancomycin dose to 0.2 g，q8 h. All the above suggestions were adopted by doctors. And the child ’s body temperature dropped after treatment ，the blood culture turned negative and laboratory indicators returned to normal. The child was discharged smoothly. CONCLUSIONS ：Infants and young children are special groups. Therefore ，before using antibiotics ，clinical pharmacists should evaluate the age ，body weight ，liver and kidney functions of infants and young children. They should also help doctors select and adjust drugs ，frequency and dosage on the basis of pharmacokinetic characteristics and safety ，so as to avoid adverse drug reactions while ensure curative effect.

Role of Clinical Pharmacists in Anti-infective Therapy for Patients with Septic Shock in ICU / 中国药房

OBJECTIVE：To explore the role of clinical pharm acists in anti-infective therapy in patients with septic shock in the ICU. METHODS ：A total of 180 patients with septic shock were retrospectively collected from ICU of Chongqing Qianjiang Central Hospital during Jan.-Dec. 2018. According to whether clinical pharmacists participated in anti-infective therapy in the whole process，the patients were divided into intervention group （92 cases）and control group （88 cases）. Both groups were given routine treatment according to clinical diagnosis ；on this basis ，clinical pharmacists participated in the whole anti-infective therapy of the intervention group ，including participating in pharmaceutical rounds ，formulating anti-infective programs ，guiding nurses to implement anti-infective plan ，and providing pharmaceutical care for patients. The effectiveness ，safety and antibiotics clinical use indexes（such as proportion ，treatment course and cost of key monitored drugs ）were evaluated in 2 groups. RESULTS ：The cure rate of intervention group （98.91％）was significantly higher than that of control group （93.18％），while the incidence of ADR in the intervention group （8.70％）was significantly lower than control group （23.86％）. The use of antibiotics types was more rational（the proportion of carbapenems used in intervention group and control group were 20.65％，36.36％；those of quinolones were 15.22％，28.41％，respectively）；the duration of antibiotics use in the intervention group [ （15.18±2.25）d] was significantly shorter than control group [ （19.84±3.81）d]. The cost of antibiotics per capita [ （2 846.99±712.48）yuan] was significantly lower than control group [ （3 991.26±577.82）yuan]，with statistical significance of all above （P＜0.05 or P＜0.01）. CONCLUSIONS ： Clinical pharmacists participating in the anti-infective treatment of ICU patients with septic shock and providing pharmaceutical care，can improve the anti-infective effect ，reduce adverse drug reactions and drug-induced diseases ，optimize the use of antibiotics and reduce medical cost.

Sevoflurano tópico como tratamiento analgésico y antimicrobiano de tenosinovitis piógena de los flexores de la mano. Caso clínico / Topical sevoflurane as analgesic and antimicrobial treatment of pyogenic flexor tenosynovitis of the hand. Case report

Presentamos el caso de un paciente con una tenosinovitis piógena del 5° dedo de la mano, tratado inicialmente con desbridamiento quirúrgico y antibioterapia empírica. La evolución fue desfavorable, pues el dedo presentaba un defecto de cobertura con signos infecciosos en la herida y las curas resultaban muy dolorosas. Al paciente se le ofertaron varias opciones quirúrgicas y, mientras se decidía por alguna, aceptó por escrito iniciar curas con sevoflurano líquido tópico (según protocolo vigente para uso de fármacos fuera de indicación). El efecto analgésico del sevoflurano apareció rápidamente, y la evolución posterior de la herida fue muy favorable, pues los signos infecciosos desaparecieron y el defecto de cobertura se había cerrado tras tres semanas de empleo de sevoflurano tópico, sin necesidad de nuevas cirugías. Este caso ejemplifica que el uso fuera de indicación de sevoflurano tópico para tratar heridas complejas puede evitar actuaciones quirúrgicas, mucho más agresivas para los pacientes.

The clinical case is presented on a patient suffering from pyogenic tenosynovitis affecting the 5th finger of the hand, which was initially treated with surgical debridement and empirical antibiotic treatment. The clinical outcome was unfavourable, since the finger presented with a coverage defect, and the wound seemed to be infected. Wound cleaning and dressings were very painful. The patient was asked to choose between several surgical therapeutic alternatives, but he gave written informed consent to be treated with topical sevoflurane, following an approved protocol for the off-label use of this drug. Pain was accurately controlled after sevoflurane application, and the wound exhibited a very good outcome with disappearance of the clinical signs of infection and complete closure of the defect coverage after three weeks of sevoflurane, with no new surgical procedures. The present clinical case illustrates how the off-label use of topical sevoflurane for the treatment of complicated wounds could be useful to avoid surgical procedures that are more aggressive for patients.

Pharmaceutical Care for a Case of Osteosarcoma Patient with Periprosthetic Joint Infection Provided by Clinical Pharmacist / 中国药房

OBJECTIVE： To explore the role of clinical pharmacist in individualized treatment for osteosarcoma patients with periprosthetic joint infection （PJI）. METHODS： An osteosarcoma patient was admitted to our hospital and then suffered from PJI after operation. Clinical pharmacist adjusted the initial anti-infection plan and carried out pharmaceutical care according to the results of patients’ etiology and drug sensitivity. According to the PK-PD principle， combined with the therapeutic drug monitoring （TDM）， the dose of antibiotics was adjusted. With the occurrence of ADR， the antibiotic therapeutic regimen was adjusted again. RESULTS： The patient was administrated cefotiam for empiric therapy initially after the diagnosis of PJI. After obtaining the results of etiology and drug sensitivity， the clinical pharmacist suggested that vancomycin sensitive to penicillin-resistant Staphylococcus epidermidis should be used for targeted anti-infection treatment. After adjusting the dosage according to the steady-state valley concentration， the patient had slight liver function damage， accompanied with chest tightness and shortness of breath. After analysis， the clinical pharmacist considered the adverse drug reactions related to vancomycin， and again suggested that the patient should be treated with teicoplanin. After the doctor adopted the treatment plan recommended by the clinical pharmacist， PJI of the patient was effectively controlled， and the adverse reaction symptoms disappeared. The patient was effectively cured for PJI and discharged eventually. During the treatment period， the clinical pharmacist also carried out medication education for the drugs used by the patient. CONCLUSIONS： Clinical pharmacist should master the principle of antibiotic drug PK-PD theory and evaluate the clinical efficacy and safety of anti-infective drugs dynamically based on the guidance of TDM， so as to develop individualized anti-infection therapeutic regimen for osteosarcoma patient with PJI， improve the effect of clinical treatment and guarantee the safety of drug use.

Optimization of Anti-infective Program for A Obese Patient with Pulmonary Infection after Stroke by Clinical Pharmacists / 中国药房

OBJECTIVE： To explore the methods and ideas for clinical pharmacists to optimize anti-infective treatment programs in obese patients with pulmonary infection. METHODS： The clinical pharmacist optimized the anti-infection regimen of an obese patient with post-stroke pulmonary infection （BMI＝34.602 kg/m2） admitted to our hospital， and adjusted the dose adjustment and drug replacement of piperacillin tazobactam in the obese patient. And the selection of methicillin-resistant Staphylococcus aureus （MRSA） drugs and dose determination were proposed. RESULTS： According to the patient’s body weight and guidelines， the dose of piperacillin tazobactam was adjusted from 4.5 g， q12 h to 4.5 g， q6 h； the antibiotic was changed to moxifloxacin due to pathogenic changes， the dose was 0.4 g， qd， no need to increase When diagnosed as pneumonia caused by MRSA infection， linezolid was used instead of vancomycin for infection treatment in obese patients， and the dose was determined to be 600 mg， q12 h. The physician adopted the above recommendations. After treatment， the patient’s temperature decreased， cough and sputum eased， and the laboratory indicators returned to normal and discharged smoothly. CONCLUSION： Clinical pharmacists can participate in the drug treatment of special obese patients by exerting their own professional advantages： by adjusting the type， dose and frequency of antibacterial drugs， patients can obtain individualized treatment， improve the safety and effectiveness of patients’ medication， and finally obtain satisfactory results.

Constituent and effects of polysaccharides isolated from Sophora moorcroftiana seeds on lifespan, reproduction, stress resistance, and antimicrobial capacity in Caenorhabditis elegans / 中国天然药物

Sophora moorcroftiana (S. moorcroftiana) is an endemic leguminous dwarf shrub in Tibet, China. Decoctions of the seeds have been used in Chinese folk medicine for dephlogistication, detoxication, and infectious diseases. The present study aimed to investigate the constituent and biological effects of polysaccharides from S. moorcroftiana seeds in Caenorhabditis elegans (C. elegans). Polysaccharides from S. moorcroftiana seeds (SMpol) were extracted with 60% ethanol and constituent was analyzed by GC-MS. SMpol was composed of glucose, galactose and inositol in the molar ratio of 35.7 : 1.3 : 17.0. Synchronized worms were treated with SMpol and then lifespan, motility, reproduction, stress resistance and antimicrobial activity were examined. Compared with the control group, the lifespan was increased to the average of 27.3 days and the number of laying eggs showed a 1.3-fold increase in nematodes treated with SMpol (4 mg·mL). In SMpol (4 mg·mL) treated worms, there was a 1.1-fold increase in 24-h survival of acute heat stress and a 1.6-fold increase in 2-h survival of oxidative stress The colonization of the bacteria in the SMpol treated nematode was significantly lower than that of the untreated group by 68.3%. In vivo studies showed SMpol significantly extended the life span, improved reproduction, increased stress resistance and antimicrobial capacity of C. elegans. In conclusion, those results indicated that the polysaccharides from S. moorcroftiana seeds were involved in a variety of biological activities leading to its modulatory effects on C. elegans which may be developed as a natural supplement agent.

Anti-Infective Pharmaceutical Care of Critically III Patients / 中国药学杂志

OBJECTIVE: Discuss the importance of clinical pharmacists and pharmacy care during anti-infective therapy in critically ill patients. METHODS: Clinical pharmacists involved in the treatment process of a case of critically ill patients, who has craniocerebral injury, multiple organ insufficiency, severe infection, electrolyte imbalance, venous thrombosis of both lower extremities, anemia, and gastrointestinal bleeding. Pharmacy care includes adjustment of anti-infective treatment, reduce adverse drug reactions and maintain homeostasis, et al. RESULTS: The patient was cured and in a stable condition after systematic treatment. CONCLUSION: Clinical pharmacists could play an important role in improving the prognosis of critically ill patients.

Surface modification of orthopaedic titanium implant for anti-infection and promoting fracture healing: An update / 第二军医大学学报

Orthopaedic implants in the body brings a high risk of microbial infections. Infection is one of the main reasons for failure of implant in department of orthopaedics, and is more common in open fracture surgery. Fracture nonunion after internal fixations is not rare clinically, and reoperation or even multi-operations are required, which will be a heavy burden for the patients physically, mentally and economically. The aggregation and activation of macrophages can increase the cell count around the implants, which improves the immune function of the implant/tissue interface, thus contributing to prevention or treatment of infection. In addition, surface modification of titanium and its alloys, and loading antibiotics or bioactive substances also play a role in prevention or treatment of infection and nonunion. This review summarizes the current research on anti-infection function and fracture healing promotion in the surface modification of titanium and its alloys, so as to provide references for designing orthopaedic implants with anti-infection and fracture healing promotion functions.

Pharmaceutical Care of MODS Patient Treated by Continuous Renal Replacement Therapy / 医药导报

Objective To discuss the contribution of clinical pharmacists in anti-infection treatment of a patient with multiple organ dysfunction syndrome ( MODS) undergoing continuous renal replacement therapy ( CRRT). Methods Pharmacists participated in the anti-infection treatment of a MODS patient undergoing CRRT.Pharmacists assisted physicians in optimizing the therapeutic regimen based on treatment guidelines and relative information. Results Physicians accepted the advice of pharmacists after comprehensive evaluation.Ten days later,the patient recovered from shock,as the infection indexes were improved significantly.He then moved back to the general ward. Conclusion Pharmacists should positively participate in clinical treatment with physicians,in order to play a critical role in ensuring the safety and efficacy of the medication.

Clinical treatment and experience of treating allogeneic lung transplantation with different ABO blood groups / 天津医药

Objective To summarize the clinical experience in the treatment of allogeneic lung transplantation with ABO-different donor. Methods Data of three cases of lung transplantation carried out in Tianjin First Central Hospital from August to September 2015 were retrospectively analysed. ABO blood groups were different but compatible in three donors who were with brain death, and their panel reactive antibody (PRA) and lymphocyte poison cross matching test were negative. The surgical approaches were left single-lung transplantation and sequential bilateral single-lung transplantation. After the surgery, measures for pneumonedema control, immuno suppression (mycophenolate mofetil + tacrolimus +glucocorticoids) and anti-infection (imipenem and cilastatin sodium+ micafungin sodium+ganciclovir) were carried out. Results The operation wsa completed successfully in all 3 patients, and the operative time was 5-6 hours. The cold ischemia time was less than 4 hours. The blood loss during the operation was 800-1000 mL. The trachea cannula extubation was pulled out within 24 h, thoracic drainage tube was pulled out within 72 h. All the patients were moved into general ward in 5-8 days. Patients discharged from hospital in 5 weeks after operation. Pneumonia infection occurred in 2 cases on the 6 th day after operation, and antibiotic treatment was upgraded and infection was cured after 3 weeks. All patients were followed up for 21-22 months, and 3 patients survived without serious complications such as graft rejection. Conclusion Comprehensive and effective surgical techniques, reasonable choice of donor lung and preservation method, active anti-infection strategy and triple immunosuppressive program can improve the survival rate after transplantation.

Constituent and effects of polysaccharides isolated from Sophora moorcroftiana seeds on lifespan, reproduction, stress resistance, and antimicrobial capacity in Caenorhabditis elegans / 中国天然药物

Sophora moorcroftiana (S. moorcroftiana) is an endemic leguminous dwarf shrub in Tibet, China. Decoctions of the seeds have been used in Chinese folk medicine for dephlogistication, detoxication, and infectious diseases. The present study aimed to investigate the constituent and biological effects of polysaccharides from S. moorcroftiana seeds in Caenorhabditis elegans (C. elegans). Polysaccharides from S. moorcroftiana seeds (SMpol) were extracted with 60% ethanol and constituent was analyzed by GC-MS. SMpol was composed of glucose, galactose and inositol in the molar ratio of 35.7 : 1.3 : 17.0. Synchronized worms were treated with SMpol and then lifespan, motility, reproduction, stress resistance and antimicrobial activity were examined. Compared with the control group, the lifespan was increased to the average of 27.3 days and the number of laying eggs showed a 1.3-fold increase in nematodes treated with SMpol (4 mg·mL). In SMpol (4 mg·mL) treated worms, there was a 1.1-fold increase in 24-h survival of acute heat stress and a 1.6-fold increase in 2-h survival of oxidative stress The colonization of the bacteria in the SMpol treated nematode was significantly lower than that of the untreated group by 68.3%. In vivo studies showed SMpol significantly extended the life span, improved reproduction, increased stress resistance and antimicrobial capacity of C. elegans. In conclusion, those results indicated that the polysaccharides from S. moorcroftiana seeds were involved in a variety of biological activities leading to its modulatory effects on C. elegans which may be developed as a natural supplement agent.

Evaluation of Clinical Pharmacist Consultations and Typical Case Analysis / 医药导报

Objective To evaluate the effect of clinical pharmacists on cases consultation by retrospective analysis.Methods Seven hundred and thirty-one consultation cases from January 2011 to December 2014 were systematically reviewed, and the clinical department, question classification, organ system of infection, consultation purpose, recommendation variety to infection problems, acception percentage, infection problem outcome were recorded.Furthermore, the typical cases were analysed.Results The number of consultations and clinical departments increased by years, formulating anti-infective therapeutic regimen, determining duration of therapy and drug dosage were the main purposes of consultation.The proportion of infection problems was 86.0%, adoption rate of recommendations was 83.6%, the clinical efficacy rate was 84.3% among them.The proportion of non-infectious problems was 14.0%, adoption rate of recommendations was 100.0%.Conclusion Clinical pharmacists' professional skills are respected by doctors.Anti-infection problem is a breakthrough point for deeply developing the work of clinical pharmacists.

Anti-infective reconstituted bone xenograft combined with external fixator for treatment of posttraumatic long bone infection in lower extremities / 中华创伤杂志

Objective To observe the long-term efficacy of anti-infective reconstituted bone xenograft (ARBX) combined with external fixation of posttraumatic long bone infection in lower extremities.Methods This retrospective case series study included 36 patients with posttraumatic long bone infection in lower extremities followed up for more than 18 months after receiving one-stage ARBX bone grafting combined with ring external fixation from January 2004 to December 2013.There were 21 male and 15 female patients,at the age of 19-72 years (mean,35.8 years).Multiple fractures were seen in 24 patients and single fractures in 12 patients.Bone and functional results were evaluated using the association for the study and application of the method of Ilizarov (ASAMI) classification.Results Follow-up ranged from 18 to 72 months (mean,38 months).Bone union was seen in 33 cases in a mean period of 5.2 months,and infection was completely cured.Length of limbs in all patients reached the expected extension length with the bone extension length of 3-10 cm (mean,5.2 cm).All the extended areas showed bone healing.According to the ASAMI classification,bone result was excellent in 20 patients,good in 13 and fair in 3,with the excellent and good rate of 92％,and limb function recovery was excellent in 18 patients,good in 11 and fair in 7,with the excellent and good rate of 81％.Conclusion ARBX adjuvant external fixator treatment of posttraumatic long bone infection in lower extremities improves bone healing rate and limb function recovery rate and shortens bone healing time at one stage.

Practice and Experience of Clinical Pharmacist in Participating in the Anti-infective Treatment of Severe Patients in Urology Department / 中国药师

Objective: To investigate the role of clinical pharmacist in the treatment of patients with severe infections in urology department.Methods: An objective analysis of the important roles of clinical pharmacists was carried out by making and adjusting the anti-infective treatment plan of two patients in urology department.Results: During the participation in the treatment of two patients with severe infections in urology department, clinical pharmacists played important roles in the treatment of the diseases through observing the clinical symptoms,analyzing the conditions of the patients and giving the pharmaceutical opinions and suggestions, and finally the infections were controlled successfully.Conclusion: Clinical pharmacists should participate in the therapy strategy adjustment in urology department using their professional knowledge to play important roles in the management of anti-infection strategy for severe patients.