To introduce a strategy for a case of severe pneumonia caused by carbapenem-resistant Klebsiella pneumonia, which have failed to treat with tigecycline combined with meropenem, ceftazidime avibactam, and ceftazidime avibactam combined with aztreonam. Clinical pharmacist made anti-infective regimen based on colistin sulfate drip (750 000 units, ivd, q12h, first dose of 1.5 million units) and atomization (250 000 units, q12h) combined with tigecycline (100 mg, ivd, q12h, first dose 200 mg) according to patient’s clinical manifestations, renal function, the dynamic changes of infection indicators, metagenomics next-generation sequencing results and the PK/PD characteristics of the anti-bacterial drugs. The anti-infection regimens (intravenous plus aerosolized colistin combined with tigecycline) proposed by the clinical pharmacist were adopted by doctors and the pneumonia was effectively controlled. Clinical pharmacists played an effective role in the  clinical healthcare team by tracking frontier of antibacterial drugs, which fully embodied the professional value in optimizing treatment regimens of intractable infections.

1.杨志寅, 主编. 内科危重病, 第2版 [M]. 北京: 人民卫生出版社, 2006: 126-128.

2.中华医学会呼吸病学分会感染学组. 中国成人医院获得性肺炎与呼吸机相关性肺炎诊断和治疗指南(2018年版)[J]. 中华结核和呼吸杂志, 2018, 41(4): 255-280. DOI: 10.3760/cma.j.issn.1001-0939.2018.04.006.

3.中华医学会呼吸病学分会. 中国成人社区获得性肺炎诊断和治疗指南(2016年版)[J]. 中华结核和呼吸杂志, 2016, 39(4): 253-279. DOI: 10.3760/cma. j.issn.1001-0939.2016.04.005.

4.Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults[J]. Clin Infect Dis, 2007, 44 (Suppl 2): S27-S72. DOI: 10.1086/511159.

5.Navon-Venezia S, Kondratyeva K, Carattoli A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance[J]. FEMS Microbiol Rev, 2017, 41(3): 252-275. DOI: 10.1093/femsre/fux013.

6.中国碳青霉烯耐药肠杆菌科细菌感染诊治与防控专家共识编写组, 中国医药教育协会感染疾病专业委员会, 中华医学会细菌感染与耐药防控专业委员会. 中国碳青霉烯耐药肠杆菌科细菌感染诊治与防控专家共识[J]. 中华医学杂志, 2021, 101(36): 2850-2860. DOI: 10.3760/cma.j.cn112137-20210219-00438.

7.Gallagher P, Baker S. Developing new therapeutic approaches for treating infections caused by multi-drug resistant Acinetobacter baumannii: Acinetobacter baumannii therapeutics[J]. J Infect, 2020, 81(6): 857-861. DOI: 10.1016/j.jinf.2020.10.016.

8.Bonnin RA, Girlich D, Jousset AB, et al. A single Proteus mirabilis lineage from human and animal sources: a hidden reservoir of OXA-23 or OXA-58 carbapenemases in Enterobacterales[J]. Sci Rep, 2020, 10(1): 9160. DOI: 10.1038/s41598-020-66161-z.

9.Tamma PD, Aitken SL, Bonomo RA, et al. Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum beta-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa)[J]. Clin Infect Dis, 2021, 72(7): 1109-1116. DOI: 10.1093/cid/ciab295.

10.Satapoomin N, Dulyayangkul P, Avison MB. Klebsiella pneumoniae mutants resistant to ceftazidime-avibactam plus aztreonam, imipenem-relebactam, meropenem-vaborbactam, and cefepime-taniborbactam[J]. Antimicrob Agents Chemother, 2022, 66(4): e0217921. DOI: 10.1128/aac.02179-21.

11.Zhen S, Wang H, Feng S. Update of clinical application in ceftazidime-avibactam for multidrug-resistant Gram-negative bacteria infections[J]. Infection, 2022, 50(6): 1409-1423. DOI: 10.1007/s15010-022-01876-x.

12.Gutierrez-Gutierrez B, Salamanca E, De Cueto M, et al. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study[J]. Lancet Infect Dis, 2017, 17(7): 726-734. DOI: 10.1016/S1473-3099(17)30228-1.

13.Levy Hara G, Gould I, Endimiani A, et al. Detection, treatment, and prevention of carbapenemase-producing Enterobacteriaceae: recommendations from an International Working Group[J]. J Chemother, 2013, 25(3): 129-140. DOI: 10.1179/1973947812Y.0000000062.

14.Wang ZQ, Guo ZL, Feng H, et al. Treatment of donor-derived carbapenem-resistant Klebsiella pneumoniae infection after renal transplantation with tigecycline and extended-infusion meropenem[J]. Curr Med Sci, 2021, 41(4): 770-776. DOI: 10.1007/s11596-021-2397-z.

15.Chen D, Xiao L, Hong D, et al. Epidemiology of resistance of carbapenemase-producing Klebsiella pneumoniae to ceftazidime-avibactam in a Chinese hospital[J]. J Appl Microbiol, 2022, 132(1): 237-243. DOI: 10.1111/jam.15166.

16.Chen Y, Huang HB, Peng JM, et al. Efficacy and safety of ceftazidime-avibactam for the treatment of carbapenem-resistant Enterobacterales bloodstream infection: a systematic review and meta-analysis[J]. Microbiol Spectr, 2022, 10(2): e0260321. DOI: 10.1128/spectrum.02603-21.

17.Das S, Li J, Riccobene T, et al. Dose selection and validation for ceftazidime-avibactam in adults with complicated intra-abdominal infections, complicated urinary tract infections, and nosocomial pneumonia[J]. Antimicrob Agents Chemother, 2019, 63(4): e02187-02218. DOI: 10.1128/AAC.02187-18.

18.中国细菌耐药监测网. CHINET 2022年全年细菌耐药监测结果[EB/OL]. (2022)[2023-11-08] http://www.chinets.com/Document/Index?pageIndex=0.

19.Oliva A, Campogiani L, Savelloni G, et al. Clinical characteristics and outcome of ceftazidime/avibactam-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae infections: a retrospective, observational, 2-center clinical study[J]. Open Forum Infect Dis, 2023, 10(7): ofad327. DOI: 10.1093/ofid/ofad327.

20.Zhou J, Yang J, Hu F, et al. Clinical and molecular epidemiologic characteristics of ceftazidime/avibactam-resistant carbapenem-resistant Klebsiella pneumoniae in a neonatal intensive care unit in China[J]. Infect Drug Resist, 2020, 13: 2571-2578. DOI: 10.2147/IDR.S256922.

21.Zarras C, Iosifidis E, Simitsopoulou M, et al. Neonatal bloodstream infection with ceftazidime-avibactam-resistant bla(KPC-2)-producing Klebsiella pneumoniae carrying bla(VEB-25)[J]. Antibiotics (Basel), 2023, 12(8): 1290. DOI: 10.3390/antibiotics12081290.

22.Huang X, Shen S, Chang F, et al. Emergence of KPC-134, a KPC-2 variant associated with ceftazidime-avibactam resistance in a ST11 Klebsiella pneumoniae clinical strain[J]. Microbiol Spectr, 2023, 11(5): e0072523. DOI: 10.1128/spectrum.00725-23.

23.Zhou YF, Liu P, Zhang CJ, et al. Colistin combined with tigecycline: a promising alternative strategy to combat Escherichia coli harboring blaNDM-5 and mcr-1[J]. Front Microbiol, 2019, 10: 2957. DOI: 10.3389/fmicb.2019. 02957.

24.Ahmed MU, Velkov T, Lin YW, et al. Potential toxicity of polymyxins in human lung epithelial cells[J]. Antimicrob Agents Chemother, 2017, 61(6). DOI: 10.1128/ AAC.02690-16.

25.中国医药教育协会感染疾病专业委员会, 中华医学会呼吸病学分会, 中华医学会重症医学分会, 等. 中国多黏菌素类抗菌药物临床合理应用多学科专家共识 [J]. 中华结核和呼吸杂志, 2021, 44(4): 292-310. DOI:  10.3760/cma.j.cn112147-20201109-01091.

26.唐晓, 翟乃亮. 多黏菌素E雾化吸入用于呼吸机相关性肺炎的临床效果探究[J]. 保健文汇, 2019, (8): 182-183. [Tang X, Zhai NL. Clinical efficacy of nebulized inhalation of polymyxin E for ventilator-associated pneumonia[J]. Health Literature, 2019, (8): 182-183.] DOI: 10.3969/j.issn.1671-5217.2019.08.090.

27.陈赟, 慕心力. 多黏菌素E治疗ICU患者肺部鲍曼不动杆菌感染的临床回顾性研究[J]. 空军军医大学学报, 2022, 43(7): 871-874, 878. [Chen Y, Mu XL. A retrospective clinical study of plymyxin E in the treatment of pulmonary Acinetobacter baumannii infection in ICU patients[J]. Journal of Air Force Medical University, 2033, 43(7): 871-874, 878.] DOI: 10.13276/j.issn.2097-1656.2022.07.018.

28.孟现民, 董平, 张永信. 多黏菌素类抗生素的肾毒性[J]. 上海医药, 2015, (23): 18-21. [Meng XM, Dong P, Zhang YX. Nephrotoxicity of polymyxins[J]. Shanghai Medical & Pharmaceutical Journal, 2015, (23): 18-21.] DOI: 1006-1533(2015)23-0018-04.

29.Vardakas KZ, Voulgaris GL, Samonis G, et al. Inhaled colistin monotherapy for respiratory tract infections in adults without cystic fibrosis: a systematic review and meta-analysis[J]. Int J Antimicrob Agents, 2018, 51(1): 1-9. DOI: 10.1016/j.ijantimicag.2017.05.016.

30.李立, 叶璟, 胡蕾, 等. 雾化黏菌素的应用进展[J]. 医学综述, 2021, 27(24): 4898-4903. [Li L, Ye J, Hu L, et al. Application progress of aerosolized colistin[J]. Medical Recapitulate, 2021, 27(24): 4898-4903.] DOI: 10.3969/j.issn.1006-2084.2021.24.021.

31.Zhang C, Liu X, Wu H, et al. Proteomic response revealed signaling pathways involving in the mechanism of polymyxin B-induced melanogenesis[J]. Microbiol Spectr, 2022, 10(2): e0273021. DOI: 10.1128/spectrum.02730-21.

32.赵莹, 崔向丽, 张超, 等. 替加环素致凝血功能障碍药学监护一例[J]. 临床药物治疗杂志, 2021, 19(6): 87-89. [Zhao Y, Cui XL, Zhang C, et al. Pharmaceutical care for tigecycline-induced coagulation disorders: a case report[J]. Clinical Medication Journal, 2021, 19(6): 87-89.] DOI: 10.3969/j.issn.1672-3384.2021.06.012.

33.Kadoyama K, Sakaeda T, Tamon A, et al. Adverse event profile of tigecycline: data mining of the public version of the U.S. Food and Drug Administration adverse event reporting system[J]. Biol Pharm Bull, 2012, 35(6): 967-970. DOI: 10.1248/bpb.35.967.